Luca Giacomello

Hypercapnia and Acidosis During Open and Thoracoscopic Repair of Congenital Diaphragmatic Hernia and Esophageal Atresia Results of a Pilot Randomized Controlled Trial

Objective: We aimed to evaluate the effect of thoracoscopy in neonates on intraoperative arterial blood gases, compared with open surgery. Background: Congenital diaphragmatic hernia (CDH) and esophageal atresia with tracheoesophageal fistula (EA/TEF) can be repaired thoracoscopically, but this may cause hypercapnia and acidosis, which are potentially harmful. Methods: This was a pilot randomized controlled trial. The target number of 20 neonates (weight > 1.6 kg) were randomized to either open (5 CDH, 5 EA/TEF) or thoracoscopic (5 CDH, 5 EA/TEF) repair. Arterial blood gases were measured every 30 minutes intraoperatively, and compared by multilevel modeling, presented as mean and difference (95% confidence interval) from these predictions. Results: Overall, the intraoperative PaCO2 was 61 mm Hg in open and 83 mm Hg [difference 22 mm Hg (2 to 42); P = 0.036] in thoracoscopy and the pH was 7.24 in open and 7.13 [difference −0.11 (−0.20 to −0.01); P = 0.025] in thoracoscopy. The duration of hypercapnia and acidosis was longer in thoracoscopy compared with that in open. For patients with CDH, thoracoscopy was associated with a significant increase in intraoperative hypercapnia [open 68 mm Hg; thoracoscopy 96 mm Hg; difference 28 mm Hg (8 to 48); P = 0.008] and severe acidosis [open 7.21; thoracoscopy 7.08; difference −0.13 (−0.24 to −0.02); P = 0.018]. No significant difference in PaCO2, pH, or PaO2 was observed in patients undergoing thoracoscopic repair of EA/TEF. Conclusions: This pilot randomized controlled trial shows that thoracoscopic repair of CDH is associated with prolonged and severe intraoperative hypercapnia and acidosis, compared with open surgery. These findings do not support the use of thoracoscopy with CO2 insufflation and conventional ventilation for the repair of CDH, calling into question the safety of this practice. The effect of thoracoscopy on blood gases during repair of EA/TEF in neonates requires further evaluation. (ClinicalTrials.gov Identifier: NCT01467245)

Comparative Study of Immune Regulatory Properties of Stem Cells Derived from Different Tissues.

Allogeneic stem cell (SC)-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some SC types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow-MSCs, olfactory ectomesenchymal SCs, leptomeningeal SCs, and three different c-Kit-positive SC types, that is, amniotic fluid SCs, cardiac SCs, and lung SCs. We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers ICAM-1, VCAM-1, HLA-ABC, and HLA-DR, modulatory activity toward purified T, B, and NK cells, lower immunogenicity of inflammatory-primed SCs as compared to resting SCs, and indoleamine-2,3-dioxygenase-activation as molecular inhibitory pathways, with some SC type-related peculiarities. Moreover, the SC types analyzed exert an anti-apoptotic effect toward not-activated immune effector cells (IECs). In addition, we found that the inhibitory behavior is not a constitutive property of SCs, but is acquired as a consequence of IEC activation, as previously described for MSCs. Thus, immune regulation is a general property of SCs and the characterization of this phenomenon may be useful for a proper therapeutic use of SCs.

Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) and esophageal atresia with tracheoesophageal fistula (EA/TOF) can be repaired thoracoscopically, but this may cause hypercapnia, acidosis, and reduced cerebral oxygenation. We evaluated the effect of thoracoscopy in infants on cerebral oxygen saturation (cSO(2)), arterial blood gases, and carbon dioxide (CO(2)) absorption. METHODS Eight infants underwent thoracoscopy (6 CDH and 2 EA/TOF). Serial arterial blood gases were taken. Regional cSO(2) was measured using near-infrared spectroscopy. Absorption of insufflated CO(2) was calculated from exhaled (13)CO(2)/(12)CO(2) ratio measured by mass spectrometry. RESULTS CO(2) absorption increased during thoracoscopy with a maximum 29% ± 6% of exhaled CO(2) originating from the pneumothorax. Paco(2) increased from 9.4 ± 1.3 kPa at the start to 12.4 ± 1.0 intraoperatively and then decreased to 7.6 ± 1.2 kPa at end of operation. Arterial pH decreased from 7.19 ± 0.04 at the start to 7.05 ± 0.04 intraoperatively and then recovered to 7.28 ± 0.06 at end of operation. Cerebral hemoglobin oxygen saturation decreased from 87% ± 4% at the start to 75% ± 5% at end of operation. This had not recovered by 12 (74% ± 4%) or 24 hours (73% ± 3%) postoperatively. CONCLUSIONS This preliminary study suggests that thoracoscopic repair of CDH and EA/TOF may be associated with acidosis and decreased cSO(2). The effects of these phenomena on future brain development are unknown.

Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative ventilation and recurrence

INTRODUCTION Thoracoscopic repair of congenital diaphragmatic hernia (CDH) has been described, but its efficacy and safety have not been validated. The aim was to compare our experience of thoracoscopy with laparotomy repair. METHODS After ethics approval, we reviewed the notes of neonates with CDH operated in our institution between 2003 and 2008. Two historical groups were compared: infants who underwent laparotomy (2003-2008) or thoracoscopy (2007-2008). Data were compared by t test or Mann-Whitney tests. RESULTS Thirty-five children had open repair of CDH, and 13 had thoracoscopic repair. Groups were homogeneous for age and weight. Five (38%) neonates who had thoracoscopy were converted to open for surgical difficulties (n = 4) and O(2) desaturation (n = 1). Patch repair was used in 12 (34%) open and 6 (46%) thoracoscopic repairs. End-tidal CO(2) was significantly elevated during thoracoscopy, but this was not reflected in arterial CO(2) or pH. There were 3 (8%) recurrences after open repair and 2 (25%) after thoracoscopy (P = .19). CONCLUSION Thoracoscopic repair of CDH is feasible. Arterial blood gases should be closely monitored. Despite higher EtCO(2), conversion to open was mainly because of difficult repair. A randomized trial is necessary to assess the effect of thoracoscopy on ventilation and recurrences.

Surgical repair of incarcerated inguinal hernia in children: laparoscopic or open?

PURPOSE The management of Incarcerated Inguinal Hernia (IIH) in children is challenging and may be associated with complications. We aimed to compare the outcomes of laparoscopic vs. open repair of IIH. METHODS With institutional ethical approval (09SG13), we reviewed the notes of 63 consecutive children who were admitted to a single hospital with the diagnosis of IIH between 2000 and 2008. Data are reported as median (range). Groups were compared by chi-squared or t-tests as appropriate. RESULTS · Open repair (n=35): There were 21 children with right and 14 with left IIH. 2 patients also had contralateral reducible inguinal hernia. Small bowel resection was required in 2 children. · Laparoscopic repair (n=28): All children had unilateral IIH (19 right sided, 9 left sided). 15 children (54%) with no clinical evidence of contralateral hernia, had contralateral patent processus vaginalis at laparoscopy, which was also repaired. The groups were similar with regard to gender, age at surgery, history of prematurity, interval between admission and surgery, and proportion of patients with successful preoperative manual reduction. However, the duration of operation was longer in the laparoscopy group (p=0.01). Time to full feeds and length of hospital stay were similar in both groups. Postoperative follow-up was 3.5 months (1-36), which was similar in both groups. 5 patients in the group undergoing open repair had serious complications: 1 vas transaction, 1 acquired undescended testis, 2 testicular atrophy and 1 recurrence. The laparoscopic group had a single recurrence. CONCLUSION Open repair of incarcerated inguinal hernia is associated with serious complications. The laparoscopic technique appears safe, avoids the difficult dissection of an oedematous sac in the groin, allows inspection of the reduced hernia content and permits the repair of a contralateral patent processus vaginalis if present.

Varicocele and Retrograde Adrenal Metabolites Flow

Background: Idiopathic varicocele is one of the causes of potentially correctable male subfertility. The mechanisms causing spermatogenesis impairment have yet to be clarified. The aim of this study is to analyze the effects of renal and adrenal metabolite reflux on testicular exocrine function in a rat experimental model. Materials and Methods: In the study, 45 male Lewis Stock adult rats, each weighing 300 g, were used. The rats were subdivided into three groups of 15 rats. In group A (control group) testicular volume and basal follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured at the beginning of the study and after 9 months. In group B, varicocele was induced by means of rings introduced in the left renal vein in order to cause a renospermatic reflux. In group C, similarly to group B, varicocele was induced after removal of left adrenal gland. The effects of varicocele on testicular function were then analyzed 3, 6 and 9 months after surgery. After 9 months, all rats underwent testicular biopsy. Results: Both groups B and C showed a reduction in testicular volume, an increase in FSH and a decrease in testosterone levels. These levels were higher in group B. Testicular histological assessment showed important structural abnormalities in group B rats. Conclusions: These data support the hypothesis that renal and adrenal metabolites enhance varicocele-induced testicular damage. This theory is supported both by hormonal impairment and testicular histological analysis.

Secondary omental torsion in children: report of two cases and review of the literature.

Abstract Torsion of the greater omentum (TGO) may be due to a congenital abnormal attachment of its free edge. There are no specific symptoms that allow a preoperative differential diagnosis of this condition from common pathologies such as acute appendicitis. Attachment of the omentum to the large bowel and the absence of concomitant diseases make it possible to distinguish TGO secondary to a congenital attachment anomaly from omental infarction, primary TGO, and TGO secondary to an acquired attachment anomaly (attachment to cysts, tumours, hernias, surgical scars, or perforated bowel segments). Resection of the ischaemic portion of the omentum permits complete resolution of the clinical symptoms. The authors report two cases of TGO in children due to abnormal attachment of the greater omentum to the ascending and transverse colon, respectively.

Surgical Treatment of Chordee without Hypospadias

Objective: The aim of this study was to retrospectively assess the efficacy of the surgical techniques commonly used in three types of chordee without hypospadias (Devine and Horton classification).Methods: Twenty–six patients, ranging in age from 3 to 14 years, had chordee without hypospadias and underwent Nesbit dorsal plication (9 cases out of 12, type III), associated extensive mobilization of the urethra (10 cases out of 10, type II), and vascularized neourethra (3 cases out of 4, type I).Results: Eleven subjects undergoing follow–up investigation for the milder forms of chordee were satisfied with the outcome achieved; there was no impediment of any kind in the sex lives of 5 adult subjects. Of the 11 patients undergoing follow–up after more complex surgery for Devine and Horton type I–II chordee without hypospadias, a residual abnormal curvature was present in 4 subjects. These patients were submitted to one or more reoperations with outcomes defined as satisfactory.Conclusion: To avoid the risks of persistent chordee, the authors suggest more radical and accurate operations for the treatment of type I and II pseudohypospadias.

Diaphragmatic hernia in a pediatric emergency department.

Abstract Diaphragmatic hernia in pediatric emergency department poses a diagnostic challenge because of the acute or subtle timing of onset and the wide variety of clinical features. We describe 3 different late presentations of Bochdalek diaphragmatic hernia in a pediatric emergency department. These reports may help physicians avoid delayed diagnosis of late-presenting congenital diaphragmatic hernia, thereby reducing the risk of inappropriate treatments and life-threatening conditions in children.

Pleiotropic effects of sphingosine-1-phosphate signaling to control human chorionic mesenchymal stem cell physiology

Chorionic stem cells represent a promising opportunity for regenerative medicine. A deeper understanding of the stimuli that regulate their physiology, could lead to innovative clinical approaches. We revealed the presence of multiple sphingosine-1-phosphate (S1P) receptor isoforms in chorion-derived mesenchymal stem cells (CMSCs). Their activation simultaneously propagated from the plasma membrane through Gi and other heterotrimeric G proteins and further diverged toward extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 and protein kinase D 1. At a functional level, S1P signaling inhibited CMSC migration, while promoting proliferation. Instead, a reduction of cell density was obtained when S1P was combined to treatments that increased cAMP intracellular concentration. Such surprising reduction of cell viability was relatively specific as it was not observed with stromal stem cells from bone marrow. Neither it was observed by activating analogous G proteins with bradykinin nor by inducing cell death via a cAMP-independent pathway. S1P could thus reveal novel keys to improve CMSC differentiation programs acting on cAMP concentration. Furthermore, S1P receptor agonists/antagonists could become instrumental in favoring CMSC engraftment by controlling cell motility.