COMBINATION OF ESOPHAGEAL ATRESIA WITH TRACHEOESOPHAGEAL FISTULA AND DUODENAL ATRESIA: TREATMENT ANALYSIS OF FIFTEEN PATIENTS

The combination of duodenal atresia (DA) with esophageal atresia with tracheoesophageal fistula (EA-TEF) is a rare pathology, the frequency of which ranges from 1% to 6% of all cases of EA. Surgical treatment of the DA+EA-TEF combination always causes significant difficulties, primarily in determining the timing and stages of surgical correction. Objective of the study: to evaluate the results of treatment with a combination of DA+EA-TEF to determine the effective tactics of surgical treatment. Materials and methods of research: a retrospective, nonrandomized, uncontrolled, multicenter study was carried out. The work is based on the results of treatment of 15 newborns – 6 (40%) boys, 9 (60%) girls with a combination of DA+EA-TEF, who were treated in clinics of 6 university centers for pediatric surgery in the Russian Federation in 2015–2021. Simultaneous operations (SIMOPs) were performed in 10 (60%) patients, two-stage operations (TO) – in 5 (40%) newborns. The following criteria were taken into account: the period of antenatal (weeks) and postnatal (days) of establishing the diagnosis of obstruction of the gastrointestinal tract (GIT), gestational age (weeks), birth weight (g), weight at the time of surgery (g), type of concomitant pathology , sequence and methods of surgical treatment, terms of complete enteral feeding (days), outcomes of operations and reasons for unsatisfactory outcomes. The average gestational age of children who underwent SIMOPs was 35.1 weeks. (Q1 – 31.5, Q3 – 39; Me – 37; SD – 5.1; min/max – 25–40; 95% CI: 31.1–39.0) versus 29.8 weeks. at DO (Q1 – 29, Q3 – 30.5; Me – 30; SD – 1.0; min/max – 28–31; 95% CI: 28.4–31.6) did not differ statistically significantly (р=0.083). The mean body mass values did not have statistically significant differences (p=0.081) and amounted to 2224 g (Q1 – 1410, Q3 – 2930; Me – 2665; SD – 890.8; min/max – 760–3260; 95% CI: 1556–2926) for SIMOPs, versus 1322 g (Q1 – 1165, Q3 – 1450; Me – 1380; SD – 196; min/max – 980–1450; 95% CI: 1078.4–16565) in the TO group. Results: the average duration of SIMOPs was on average 144.4 min (Q1 – 125, Q3 – 155; Me – 147.5; SD – 22; min/max – 120–190; 95% CI: 1321–159.3), TO – 147.0 (Q1 – 125, Q3 – 172; Me – 140; SD – 33.4; min/max – 120–205; 95% CI: 126–178.6). The sequence of surgical correction of defects in SIMOPs in 8 (53%) patients consisted of thoracotomy, ligation of the TEF, direct anastomosis of the esophagus and the imposition of duodeno-duodenoanstomosis (DDA). In one case, DDA was selected as the first operation, which was supplemented with Kader gastrostomy followed by thoracotomy, ligation of the TEF and anastomosis of the esophagus after elongation according to I. Livaditis. In one patient, after thoracotomy and ligation of the TEF in connection with an insurmountable diastasis of the esophagus, a cervical esophagostomy (CE), duodenojejunoanastomosis (DEA) and a gastrostomy according to Kader were applied. In a two-stage correction (TO), the first operation in 3 patients was DDA (20%), supplemented in one case (7%) with Kader gastrostomy, and the second stage after 2 days performed thoracotomy with the elimination of TEF and EA. In 2 (13%) newborns, the first stage was thoracotomy, elimination of TEF and EA, followed by imposition of DDA 2 days later. In one case, due to an insurmountable diastasis of the esophagus after thoracotomy and ligation of the TEF, intrathoracic elongation of the esophagus according to Foker with delayed anastomosis of the esophagus (on the 7th day) and laparoscopic fundoplication according to Nissen (at 5 months) were performed. The duration of hospitalization did not statistically significantly depend on the chosen method for correcting the combination of DA+EA-TEF (p=0.79) and averaged 28.4 days for SIMOPs (Q1 – 16, Q3 –34.5; Me – 26; SD – 21.4; min/max – 5.0–79; 95% CI: 17.6–42.4), and for TOs – 27,2 days (Q1 – 21, Q3 – 33; Me – 28; SD – 7.1; min/max – 19–38; 95% CI: 27.2–33). In the group of patients with SIMOPs, 2 deaths (13%) were recorded on the 5th and 7th days after surgery due to progressive multiple organ failure and intractable pulmonary hypertension. In one case (7%), a lethal outcome was recorded 8 months after primary surgery due to progressive cardiovascular failure. Early postoperative mortality after SIMOPs was 20%, overall mortality was 30%. In the TO group, 3 (20%) deaths were recorded: 2 in the early postoperative period (on day 3 and day 19) and one at the age of 3 months of life. Early postoperative mortality after TO was 40%, overall mortality – 60%. Conclusion: it is preferable to choose the ligation of the TEF as the first operation and, if the child's condition allows, to impose an esophageal anastomosis and restore duodenal patency, followed by a nasogastric tube through the esophageal anastomosis into the stomach. If, after ligation of the TEF, the patient's cardiorespiratory status does not stabilize, it is possible to restore the patency of the esophagus and pass the probe into the stomach without imposing a gastrostomy, which will allow the patient to be further treated as an isolated DA, and the operation to restore the patency of the duodenum is delayed. In the presence of insurmountable diastasis, the use of esophageal elongation technology with subsequent delayed EA is justified.

Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell–Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report

Background Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. Results We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”. Conclusions In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.

The Financial Burden of Surgery for Congenital Malformations—The Austrian Perspective

Neonatal “surgical” malformations are associated with higher costs than major “non-surgical” birth defects. We aimed to analyze the financial burden on the Austrian health system of five congenital malformations requiring timely postnatal surgery. The database of the Austrian National Public Health Institute for the period from 2002 to 2014 was reviewed. Diagnosis-related group (DRG) points assigned to hospital admissions containing five congenital malformations coded as principal diagnosis (esophageal atresia, duodenal atresia, congenital diaphragmatic hernia, gastroschisis, and omphalocele) were collected and compared to all hospitalizations for other reasons. Out of 3,518,625 total hospitalizations, there were 1664 admissions of patients with the selected malformations. The annual mean number was 128 (SD 17, range 110–175). The mean cost of the congenital malformations per hospital admission expressed in DRG points was 26,588 (range 0–465,772, SD 40,702) and was significantly higher compared to the other hospitalizations (n = 3,516,961; mean DRG 2194, range 0–834,997; SD 6161; p < 0.05). Surgical conditions requiring timely postnatal surgery place a significant financial burden on the healthcare system. The creation of a dedicated national register could allow for better planning of resource allocation, for improving the outcome of affected children, and for optimizing costs.