Expression of Protein SOX9 in Biliary Atresia.

OBJECTIVES: Biliary atresia (BA) is still an enigmatic disease. Deeper knowledge of its pathophysiology could help develop better treatments. SOX9 regulates bile duct development, liver regeneration and fibrosis; therefore, it could be determinant in characterizing BA liver damage. Aim: To study if there is a SOX9 expression pattern in liver biopsies from BA patients. METHODS: Liver biopsies from BA patients (group BA), from age-matched infants without primary hepatic disease (group Control), and from patients with other liver conditions (group OLC) were compared. Expression of SOX9 was checked for: amount, intensity of immunoreaction, localization within ductular structures, perifibrotic epithelial cells, and lobular cells. The scores were added to create a scale from 0 to 11 that allowed group comparison. SOX9 Scale and liver survival were also looked for a correlation. RESULTS: All BA cases had a score >4, while all controls scored <4. OLC livers scored 1 to 8 (3.5 ±â€Š2.0) (P < 0.001 between all groups). A cut-off at 4 had 100% sensitivity and 88.24% specificity to differentiate BA from Controls and from OLC (area under receiver operating characteristic curve: 0.9989 (95% confidence interval: 0.9964-1.000). Strong expression of SOX9 was observed mainly in the nuclei of proliferated ductules of portal spaces and fibrotic bridges. SOX9 Scale score could not be related to liver survival in this study. CONCLUSION: In BA livers, SOX9 is mainly expressed in reactive ductular epithelium, following a pattern significantly different from that seen in non-BA patients; thus, SOX9 Scale may have a role in the diagnosis of BA.

Extra-axial sacral soft tissue giant cell ependymoma affecting a child: Case report and review of the literature.

An otherwise healthy eight-year-old girl presented with a mass in the soft tissue of the sacral region. The lesion was diagnosed as a vascular malformation on imaging studies, for which percutaneous sclerotherapy was attempted. The mass continued to grow and a complete resection was performed after four years. The pathological diagnosis was giant cell ependymoma (GCE). GCE is a term used to describe a rare histologic variant of ependymoma characterized by malignancy-like morphologic phenotype and indolent behavior. To the best of our knowledge, this is the first case of extra-axial soft tissue sacral GCE reported in a child.

Midline Cervical Cleft: An Anatomical Finding and a Proposal for a New Approach.

Congenital midline cervical cleft is a rare malformation. Typical case shows an area of hypotrophic skin, a cranial nipple-like structure, and a caudal blind sinus. Cervical extension is limited. Relapse of the retraction is common following cutaneous z-plasty. The aim of this study is to describe the radiological, surgical, and histological findings of the 4 cases treated in our center in the last 8 years and communicate the finding of a contractile structure, anterior to the platysma, composed by striated muscle, figure not previously described. This distinct muscular band is responsible for neck retraction. Removal of this releases cervical tension and is essential to avoid the relapse.

Auricular Reconstructive Surgery Improvement to the Firmin Technique for Placing an Earring.

Microtia has an incidence of 1 in 7000 to 8000 births. Ear reconstruction has 2 main aims: reconstructive and aesthetic, and a considerable number of patients ask for an earring at the end of their treatment. Herein, we explain our team's modification to the Firmin technique, perforating the lowest part of the autologous cartilage framework (Parri's modification). The orifice is cartilaginous and the skin covering both sides is easily perforable without contacting the rest of the framework. In conclusion, our modification for placing an earring is simple; it does not increase the surgical time and contributes to approach the perfection of auricular reconstructive surgery.

Psychometric findings and normative values for the CLEFT-Q based on 2434 children and young adult patients with cleft lip and/or palate from 12 countries.

BACKGROUND: Patients with cleft lip and/or palate can undergo numerous procedures to improve appearance, speech, dentition and hearing. We developed a cleft-specific patient-reported outcome instrument to facilitate rigorous international measurement and benchmarking. METHODS: Data were collected from patients aged 8-29 years with cleft lip and/or palate at 30 hospitals in 12 countries between October 2014 and November 2016. Rasch measurement theory analysis was used to refine the scales and to examine reliability and validity. Normative CLEFT-Q values were computed for age, sex and cleft type. RESULTS: Analysis led to the refinement of an eating and drinking checklist and 12 scales measuring appearance (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health-related quality of life (psychological, social, school, speech distress) and speech function. All scales met the requirements of the Rasch model. Analysis to explore differential item functioning by age, sex and country provided evidence to support the use of a common scoring algorithm for each scale for international use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech problem, being unhappy with facial appearance, and needing future cleft-related treatments, providing evidence of construct validity. Normative values for age, sex and cleft type showed poorer outcomes associated with older age, female sex and having a visible cleft. INTERPRETATION: The CLEFT-Q represents a rigorously developed instrument that can be used internationally to collect and compare evidence-based outcomes data from patients aged 8-29 years of age with cleft lip and/or palate.

A Standard Set of Outcome Measures for the Comprehensive Appraisal of Cleft Care.

Care of the patient with cleft lip and/or palate remains complex. Prior attempts at aggregating data to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards. There exists a critical need to better define the outcomes-particularly those that matter most to patients and their families-and to standardize the methods by which these outcomes will be measured. This report summarizes the recommendations of an international, multidisciplinary working group with regard to which outcomes a typical cleft team could track, how those outcomes could be measured and recorded, and what strategies may be employed to sustainably implement a system for prospective data collection. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of cleft care that intercenter comparisons can become possible. This is important for quality-improvement endeavors, comparative effectiveness research, and value-based health-care reform.

Airway and vascular maturation stimulated by tracheal occlusion do not correlate in the rabbit model of diaphragmatic hernia.

BACKGROUND: In animal models of congenital diaphragmatic hernia (CDH), tracheal occlusion (TO) has induced maturation of both airway spaces and vascular structures. Airway and vascular response to TO are assumed to occur in parallel. This study aims to describe and measure the relationship between airway and vascular maturation induced by TO. METHODS: A rabbit model of CDH on gestational day (GD) 23 and TO on GD 28 (term = GD 31) has been used. Two study groups have been defined: DH (diaphragmatic hernia) and TO (DH treated with TO). Animals were collected on GD 30 and blood flow data of the pulmonary artery (pulsatility index (PI) and fractional moving blood volume) were ultrasonographically measured. Lung morphometry consisted of measurements of radial alveolar count (RAC) and arterial muscular thickness. RESULTS: Animals in the DH group (n = 9) had the worst hemodynamic parameters; their lungs were hypoplastic and had the thickest arterial muscular layer. Animals in the TO group (n = 10) had all these effects reversed. There were no correlations among hemodynamic, airway, and vascular parameters, except for RAC and PI (r = -0.528, P = 0.043). CONCLUSION: Airway and vascular maturation after TO appear to be uncorrelated effects. TO could trigger several pathways that separately regulate airway and vascular responses.

Antiangiogenic treatment as a pre-operative management of alveolar soft-part sarcoma.

Alveolar soft-part sarcoma (ASPS) is a rare tumor. Cure is based solely on radical surgery. The general prognosis is poor. The tongue is an unusual site in adults, but not in children. Tumor removal can cause a severe impact on quality of life, even if reconstruction is possible. ASPS is a highly vascularized tumor and antiangiogenic therapy may have a role. We describe the use of the antiangiogenic combination bevacizumab and celecoxib in the preoperative management of a patient with an ASPS of the tongue.

Lung tissue blood perfusion changes induced by in utero tracheal occlusion in a rabbit model of congenital diaphragmatic hernia.

OBJECTIVE: To analyze the impact of in utero tracheal occlusion (TO) on lung tissue blood perfusion, as measured by fractional moving blood volume (FMBV) and conventional spectral Doppler, in a rabbit model of congenital diaphragmatic hernia (CDH). METHODS: In 50 fetal rabbits, a left CDH was surgically created at 23 days of gestational age (GA). At 28 days of GA, the surviving CDH fetuses were randomly assigned to undergo either TO (CDH+TO group) or a sham operation (CDH group). Twenty littermates, which were not operated on, served as internal normal controls. At 30 days of GA, lung perfusion estimated by FMBV and spectral Doppler of the proximal intrapulmonary artery were evaluated in the right lung during cesarean section. Doppler waveform analysis included the pulsatility index (PI), peak early diastolic reverse flow and peak systolic velocity. RESULTS: Eleven CDH fetuses, 9 CDH+TO and 20 controls were suitable for the study. CDH fetuses showed a significantly higher PI [8.0 (SD 1.8) vs. 5.22 (SD 1.1), p < 0.001] and lower FMBV [13.5% (SD 4.6) vs. 23.0% (SD 2.1), p < 0.001] than the controls. In contrast, CDH+TO fetuses had a significantly lower PI [5.8 (SD 2.3) vs. 8.0 (SD 1.8), p = 0.015] and higher FMBV [27.6% (SD 7.1) vs. 13.5% (SD 4.6), p < 0.001] than CDH fetuses, with values similar to the controls. Peak early diastolic reverse flow and peak systolic velocity showed nonsignificant differences among the study groups. The lung to body weight ratio at necropsy correlated positively with lung FMBV (r = 0.60, p < 0.001) and negatively with the pulmonary artery PI (r = -0.48, p < 0.01). CONCLUSION: Tracheal occlusion is consistently associated with increased lung tissue perfusion and decreased intrapulmonary impedance in a rabbit model of CDH.

Bilateral hydrosalpinx in patients with Hirschsprung's disease.

PURPOSE: Hirschsprung's disease (HD) is uncommon in females. There are very few reports on the patients' obstetric and gynecological outcome. Hydrosalpinx causes pain and infertility. It is rare in nonsexually active teenagers. It may be because of an intrinsic disease of the fallopian tubes or secondary to surgery. AIM: to describe the relationship between hydrosalpinx and HD or its surgical approach; to report the impact of bilateral hydrosalpinx on fertility in HD. METHODS: The records of all females with HD since 1980 were reviewed. Only patients who reached menarche were included. Prevalence of hydrosalpinx and hydrosalpinx-free survival were compared after abdominoperineal (A) or transanal (T) surgery. Treatment for hydrosalpinx was reviewed. RESULTS: Seventeen out of 27 patients had reached menarche (Group A: 13 patients; Group T: 4 patients). Five patients in group A and none in group T presented bilateral hydrosalpinx (p=0.261). There were no statistical differences in hydrosalpinx-free survival between groups (p=0.344). Hydrosalpinx treatment: two bilateral and one unilateral salpingectomy, one pyosalpinx evacuation and one untreated. Three patients had conception desire: one has children; two are on IVF program. CONCLUSION: An association between hydrosalpinx and HD was observed. The development of hydrosalpinx was not associated with surgical approach in our study. Females with HD should have a gynecological follow-up for the development of hydrosalpinx, which can impair fertility. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.

Use of angioembolization as an effective technique for the management of pediatric solid tumors.

PURPOSE: In oncology practice, angioembolization has been reported for tumor reduction before surgery, treatment of life-threatening conditions, and for palliative care. Nevertheless, the overall experience with angioembolization for the treatment of tumors is limited. We report our experience in 7 nonvascular solid pediatric tumors. MATERIALS AND METHODS: A retrospective review was carried out of medical records from pediatric patients (0-18 years) with solid nonvascular tumors who underwent angioembolization in the last 5 years at our institution. RESULTS: Seven patients underwent embolization: 2 neuroblastomas, 1 metastatic paraganglioma, 1 hepatoblastoma, 1 myofibroblastic tumor, 1 osteosarcoma, and 1 undifferentiated sarcoma. The reason for angioembolization was preparation for surgery (3), treatment of a life-threatening event (1), or palliative care (3). Each case is presented and discussed. The outcome was subsequent complete surgical resection in 3 cases, tumor vanished in 1 case, symptom control was achieved in 1, and the other 2 patients improved their survival and quality of life, however, died of disease progression. CONCLUSIONS: Tumor angioembolization may enter the treatment algorithm for selected patients who have to face difficult or unwarranted surgical procedures or have diseases where conventional therapies have failed.

False positives in the prenatal ultrasound screening of fetal structural anomalies.

OBJECTIVE: To describe the false-positive diagnoses of prenatal ultrasound screening of fetal structural anomalies. METHODS: Pregnancies with fetal structural anomalies either detected prenatally in our center or referred to us, were registered, evaluated, and followed-up prospectively by a multidisciplinary Congenital Defects Committee. After postnatal follow-up was completed, cases were assigned as true positives, false positives or false negatives and categorized by anatomical systems. Pregnancies referred with a nonconfirmed suspicion of anomaly were not included. The false-positive diagnoses were analyzed. RESULTS: From 1994 to 2004, 903 new registry entries of fetuses structurally abnormal at ultrasound with a complete follow-up were included in the Committee database. There were 76 false positives, accounting for 9.3% of all the prenatally established diagnoses. The urinary tract anomalies were the most frequent false-positive diagnoses found (n = 25; accounting for 8.7% of the urinary tract defects), but the genital anomalies showed the higher rate of no confirmation (n = 5; 15.2%). The specific anomalies most commonly not confirmed were renal pyelectasis (n = 9), cerebral ventriculomegaly (n = 9), abdominal cysts (n = 7) and short limbs (n = 7). CONCLUSION: Several prenatally diagnosed anomalies would benefit from prudent counseling, because they may be normal variants or transient findings.

Prenatal covering of the spinal cord decreases neurologic sequelae in a myelomeningocele model.

BACKGROUND/PURPOSE: Recent experience in fetal surgery to correct myelomeningocele in humans reports an early reversion of hydrocephalus and decreased need of ventricular shunting in the first months of life; however, it has not been possible to demonstrate benefit in lower extremity function. In the present work, we have tried to ascertain the impact of cord exposure on hind limb function. METHODS: Fetal rabbits with myelomeningocele (group M), treated myelomeningocele (group T), and control animals (group C) were compared at birth regarding physical examination, somatosensory-evoked potentials of the hind limbs, ventricular morphometry, and spine histology. RESULTS: No major difference was found between groups M and T in the physical examination. Somatosensory-evoked potentials of the hind limbs were absent in group M and present in group T, although showing a longer latency period and decreased amplitude than controls. The area of the third ventricle was significantly larger in group M than in group C; in group T, it was also somewhat larger but not significantly so. Cord histology had evident changes in group M and minor changes in group T, which resembled normal group C cord. CONCLUSIONS: Prenatal covering of the spinal cord prevents central and peripheral neurologic deterioration in this animal model of myelomeningocele.

Myofibroblastic tumor causing severe neonatal distress. Successful surgical resection after embolization.

This report describes a case of a term male 3.1 kg, normal delivery, 38 weeks of gestation with a record of hydramnios by prenatal sonography. He had fetal acute suffering and respiratory distress. The first radiographic study showed a mass filling the whole left thorax cage causing erosion of the inferior edge of the third rib. The mediastinum was displaced to the right. Computed tomography scan confirmed a homogeneous tumor that filled the left thorax and displaced the mediastinum to the right without invasion. Surgical biopsy informed of a highly vascularized mesenchymal tumor. The tumor was embolized with Ivalon microparticles obtaining a nearly avascular mass. Complete surgical excision was made, including the whole mass and costal segments. Microscopically, it was an inflammatory myofibroblastic tumor. It was composed mainly of spindle-shaped cells without malignant features. On immunohistochemistry, the tumor showed positive staining for vimentin, whereas antidesmin antibodies and S-100 protein were negative. The aim of this article is to present an extremely uncommon case of neonatal distress caused by an intrathoracic, extrapulmonary myofibroblastic tumor. Complete surgical resection was possible after embolization.

Congenital epigastric evisceration: a case report.

A rare case of abdominal wall defect at the epigastric midline is presented. This newborn boy had only the greater omentum eviscerated, and no other abnormalities could be detected. This case does not seem to relate to the abdominal wall defects reported so far in the literature. This singular case contributes to enlarge the spectrum of congenital defects of the abdominal wall.

Morphology and mucosal biochemistry of gastroschisis intestine in urine-free amniotic fluid.

BACKGROUND/PURPOSE: The aim of this study was to determine the role of urine exposure in gastroschisis on the pathologic and biochemical aspects. METHODS: The intestines of fetal rabbits with gastroschisis (group G), gastroschisis and urethral ligation (group GL), and normal controls (group C) were studied by measuring weigh and length, intestinal diameter and wall thickness, and thickness of each intestinal layer. Number and length of villi and villi edema were evaluated. Total protein and DNA were measured in intestinal homogenate. Lactase activity and alkaline phosphatase activity were analyzed in isolated microvilli membranes. RESULTS: Intestinal length, diameter, and wall thickness were significantly different in groups G and GL compared with C but not between groups G and GL. The same was true for the thickness of the internal muscular and serosa, villi length, and villi edema. Serosal reaction was milder in group GL than in group G, and absent in C. Total protein, lactase activity, and alkaline phosphatase activity were also significantly different in G and GL compared with C but not between G and GL. CONCLUSIONS: Urine in amniotic fluid causes an increased serosal reaction but does not account for the mucosal enzyme dysfunction.