Papers by Sanja SINDJIC-ANTUNOVIC
Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture
Journal of Pediatric Surgery

The Central European Journal of Paediatrics, Mar 1, 2020
Objective − The aim of this study was to evaluate interstitial cells of Cajal (ICC) in Hirschspru... more Objective − The aim of this study was to evaluate interstitial cells of Cajal (ICC) in Hirschsprung disease (HD), especially in children who had postsurgical problems. Material and Methods − The study included tissue samples of normoganglionic (NZ) and transitional zone (TZ) of 33 HD pediatric patients. Samples of bowel from 10 autopsy controls who did not have dysmotility were also analyzed. Hematoxylin-eosin (H&E) and immunohistochemical (MAP-2 and c-Kit (CD117)) staining were performed. Myenteric ganglia were analyzed at 5 microscopic fields H&E and MAP-2 stained sections (magnification 400×). The diameters of the submucosal nerves were measured at 3 microscopic H&E fields (magnification 400×). The ICC were analyzed on c-Kit immunostained slides at 3 microscopic fields per each bowel layer (magnification 200×): deep submucosa, circular and longitudinal muscular layer and zone of myenteric plexus. Results − The myenteric ganglion cell count was significantly lower in TZ of all children with HD, while there were no significant differences in NZ between the study group and age-matched controls. The ICC network was affected in all cases of HD. The total ICC count was significantly lower in NZ than in control (P<0.001). A critically lower ICC count (<50% of minimal ICC count in the control group) in the NZ was found in patients with postoperative problems (constipation and enterocolitis). Conclusion − Decreased count of the ICC in the NZ could be the cause of intestinal motility difficulties in the postoperative period in children with HD.

Srpski Arhiv Za Celokupno Lekarstvo, 2014
Introduction Intussusception is a common abdominal emergency in early childhood. It is idiopathic... more Introduction Intussusception is a common abdominal emergency in early childhood. It is idiopathic in more than 90% of cases with incidence of 1.5-4 per 1,000 live births. The treatment of choice is nonoperative hydrostatic or air enema reduction. Objective The aim of the study was to evaluate the influence of clinical presentation and symptom duration in non-operative treatment, considering the indications for delayed enema reduction and its efficacy. Methods From the total number of 107 patients with intusussception, aged from 2 months to 14 years (median 9 months), 102 (95%) patients with ileo-colic intussusceptions were treated initially by ultrasound guided saline enema. Records were reviewed for patients with failed initial treatment and delayed repeated enemas or operative procedure. The predictor variable included duration of presenting symptoms. Results Successful treatment by hydrostatic saline enemas had 58/102 (57%) patients. Success in reduction was greater if symptom duration was <24 hours (54/62 cases; 87%, p<0.001), compared with >24 hours, (4/45 cases; 9%). Despite failed initial attempts, enema reduction was reattempted in 12 patients, with success in 7/12 (60%) patients. Children with symptom duration >24 hours had a greater risk of requiring surgery (41/45 cases; 91%, p<0.001), including 5 (5%) patients with ileo-ileal intussusceptions. Conclusion The accuracy of ultrasound guided saline enema in intussusception reduction is high. Delay in presentation decreases success of non-operative treatment. Delayed enema reduction is important therapeutic option for intussusceptions. Surgical treatment is indicated in cases of complications.

Vojnosanitetski Pregled, 2021
Introduction/Aim. The published data indicate that the appearance of spinal deformities in childr... more Introduction/Aim. The published data indicate that the appearance of spinal deformities in children is significantly influenced by physical activity. The aim of our study was to examine the influence of physical activity on prevention and occurrence of spinal deformities in children. Methods. The study was conducted as observational, clinical study in the period from 2016-2018. Participants were children with spinal deformities, which were examined, for the first time, by physiatrists and pediatric surgeons. The sample included 100 children with spinal deformities, aged 7-17 years. The control group consisted of 100 children without spinal deformity, of similar age. The study instrument was a questionnaire based on a survey filled by children or parents/legal guardians. The questions were related to different parameters of the possible significance for the existence of spinal deformity and especially to the influence of physical activity. The collected data were processed using methods of descriptive and analytical statistics. Results. Scoliosis is the most common deformity of the spinal column, represented in about 67% (p=0.0006) of children. Respondents from both groups did not differ significantly in terms of gender. Children in the group with spinal deformities were older (11.5 ± 3.1 vs 10.4 ± 3.1 years, p=0.016), with increased body weight (43.9 ± 16.0 vs.39.3 ± 16.6 kg, p=0.046) and height (151.7 ± 17.2 vs.145.8 ± 18.2 cm, p=0.019), as well as with less physical activity (81.0% vs. 92.02%, p=0.001). Over 80% of children are regularly engaged in physical activity, more often recreationally and on average 2.5-3 hours per week. Conclusion. Children in the spinal deformity group are significantly less involved in physical activity than the control group, but there is no significant difference in the frequency and duration of time spent in physical activities during the week. It is important for children to be involved in physical activities of a recreational nature, and according to our research, 3 hours during the week.
Hernia of the umbilical cord associated with a patent omphalomesenteric duct
Journal of Postgraduate Medicine, 2017
Congenital hernia of the cord is a different type of ventral abdominal wall defect in which the b... more Congenital hernia of the cord is a different type of ventral abdominal wall defect in which the bowel usually herniates into the base of normally inserted umbilical cord through a patent umbilical ring. It is rare congenital anomaly with incidence of 1 in 5000. Although it was described as a distinct entity since 1920s it is often misdiagnosed as a small omphalocele. We present an unusal case of term male newborn with umbilical cord hernia associated with patent omphalomesenteric duct. The diagnose was made after birth despite antenatal ultrasound scans and it is managed successfully with uneventful recovery. If this is missdiagnosed, it could cause iatrogenic atresia of the ileum by clamping the umbilical cord after birth.

In Hirschsprung disease (HD) transitional zone (TZ) is interposed between aganglionic and normoga... more In Hirschsprung disease (HD) transitional zone (TZ) is interposed between aganglionic and normogan-glionic zone (NZ). Its presence on proximal resection margin could be reason for postoperative complications in HD patients. A glial cell index (GCI) is the ratio between number of glial cells and ganglion cells in enteric ganglia. The value of GCI in TZ and NZ in HD has not been evaluated previously. The aim of this study was to evaluate GCI and calretinin expression as possible additional tool in differentiation of NZ and TZ in HD. Hematoxylin-eosin and immunohistochemical (calretinin and S-100) staining were performed. NZ and TZ of HD specimens and autopsy rectal specimens were analyzed at 5 microscopic fields (magnification 400×). GCI was analyzed in both myenteric and submucosal ganglia. Myenteric GCI was significantly higher in NZ (7.0±0.64) than in TZ (4.5±1.28), irrelevant of the staining method. Mean value of myenteric GCI less than 6.0 favors TZ origin of sample. Pattern of c...

Frontiers in Pediatrics, 2020
Aim: Controversies exist on the optimal diagnostic workup for neonates with esophageal atresia (E... more Aim: Controversies exist on the optimal diagnostic workup for neonates with esophageal atresia (EA) with/without tracheoesophageal fistula (TEF). Aim of this study was to describe the current diagnostic policies in EA/TEF patients enrolled in an International multicenter registry. Methods: All patients consecutively registered from July 2014 to December 2017 in the EUPSA Esophageal Atresia Registry (EUPSA-EAR) were included in the study. Data related to diagnostic investigations among Centers forming the EUPSA-EAR were analyzed. Main Results: During the study period, 374 consecutive patients were recorded by 23 Centers. The majority of patients underwent chest X-rays, echocardiography, abdominal ultrasound, and abdominal X-rays. Preoperative bronchoscopy and esophageal gap measurement were performed in one third of the patients. Conclusions: Present data from a large cohort of patients from the EUPSA-EAR show both inter-institutional and intra-institutional variability in diagnostic workup of patients with EA/TEF. Efforts should be made to develop guidelines on the diagnostic workup for EA/TEF patients.

The Central European Journal of Paediatrics, 2020
Objective − The aim of this study was to evaluate interstitial cells of Cajal (ICC) in Hirschspru... more Objective − The aim of this study was to evaluate interstitial cells of Cajal (ICC) in Hirschsprung disease (HD), especially in children who had postsurgical problems. Material and Methods − The study included tissue samples of normoganglionic (NZ) and transitional zone (TZ) of 33 HD pediatric patients. Samples of bowel from 10 autopsy controls who did not have dysmotility were also analyzed. Hematoxylin-eosin (H&E) and immunohistochemical (MAP-2 and c-Kit (CD117)) staining were performed. Myenteric ganglia were analyzed at 5 microscopic fields H&E and MAP-2 stained sections (magnification 400×). The diameters of the submucosal nerves were measured at 3 microscopic H&E fields (magnification 400×). The ICC were analyzed on c-Kit immunostained slides at 3 microscopic fields per each bowel layer (magnification 200×): deep submucosa, circular and longitudinal muscular layer and zone of myenteric plexus. Results − The myenteric ganglion cell count was significantly lower in TZ of all children with HD, while there were no significant differences in NZ between the study group and age-matched controls. The ICC network was affected in all cases of HD. The total ICC count was significantly lower in NZ than in control (P<0.001). A critically lower ICC count (<50% of minimal ICC count in the control group) in the NZ was found in patients with postoperative problems (constipation and enterocolitis). Conclusion − Decreased count of the ICC in the NZ could be the cause of intestinal motility difficulties in the postoperative period in children with HD.

Vojnosanitetski pregled, 2019
Background/Aim. The published data indicate that the appearance of spinal deformities in children... more Background/Aim. The published data indicate that the appearance of spinal deformities in children is significantly influenced by physical activity. The aim of our study was to examine the influence of physical activity on prevention and occurrence of spinal deformities in children. Methods. The study was conducted as observational, clinical study in the period from 2016 to 2018. Participants were children with spinal deformities, which were examined, for the first time, by physiatrists and pediatric surgeons. The sample included 100 children with spinal deformities, aged 7?17 years. The control group consisted of 100 children without spinal deformity, of similar age. The study instrument was a questionnaire based on a survey filled by children or parents/legal guardians. The questions were related to different parameters of the possible significance for the existence of spinal deformity and especially to the influence of physical activity. The collected data were processed using met...
Hernia of the umbilical cord associated with a patent omphalomesenteric duct
Journal of Postgraduate Medicine, 2017
Congenital hernia of the cord is a different type of ventral abdominal wall defect in which the b... more Congenital hernia of the cord is a different type of ventral abdominal wall defect in which the bowel usually herniates into the base of normally inserted umbilical cord through a patent umbilical ring. It is rare congenital anomaly with incidence of 1 in 5000. Although it was described as a distinct entity since 1920s it is often misdiagnosed as a small omphalocele. We present an unusal case of term male newborn with umbilical cord hernia associated with patent omphalomesenteric duct. The diagnose was made after birth despite antenatal ultrasound scans and it is managed successfully with uneventful recovery. If this is missdiagnosed, it could cause iatrogenic atresia of the ileum by clamping the umbilical cord after birth.
APSP Journal of Case Reports, 2017
Thoracoschisis is a rare condition. A female newborn presented with right-sided thoracoschisis, a... more Thoracoschisis is a rare condition. A female newborn presented with right-sided thoracoschisis, associated with diaphragmatic hernia and protrusion of an accessory liver lobe through the chest wall defect along with deformity of the right forearm and hand duplication. Diagnosed as part of the limb-body wall complex (LBWC), management included resection of the exteriorized liver lobe followed by right hemidiaphragm and thoracic wall reconstruction.

Journal of Perinatal Medicine, 2016
Objective: Though the outcome for children with congenital diaphragmal hernia (CDH) is improving,... more Objective: Though the outcome for children with congenital diaphragmal hernia (CDH) is improving, management of seriously compromised respiratory and cardiovascular function remains a great challenge. The aim of this study was to review a tertiary center experience in treating children with CDH. Design: Retrospective observational study from January 2005 to December 2014. Setting: Neonatal Intensive Care Unit (NICU) of University Children Hospital (UCH), Belgrade, Serbia. Patients: Children with CDH. Results: The CDH was diagnosed prenatally in 23% patients. An overall survival rate was 62%. Among those patients who underwent surgical repair 29 (90%) survived. There was statistically significant difference in survival rate between operated patients and total examined population (P=0.020). Prenatally diagnosed neonates with CDH had significantly lower survival rate comparing to those who were postnatally diagnosed (20% vs. 75%; P=0.002). Fatal outcome was more frequent in patients wi...

Vojnosanitetski pregled, 2016
Background/Aim. Hirschsprung?s disease is the most common identifiable developmental disorder of ... more Background/Aim. Hirschsprung?s disease is the most common identifiable developmental disorder of the enteric nervous system, characterized by a failure of its formation in a variable segment of distal bowel. Currently available surgical therapies for Hirschsprung?s disease, although lifesaving, are associated with numerous complications. The aim of our study was to evaluate the effectiveness of different surgical methods and the incidence of serious complications after radical surgery of rectosigmoid Hirschsprung?s disease. Methods. A retrospective analysis, from June 1997 until May 2012 was carried out on 84 patients operated for Hirschsprung?s disease of rectosigmoid colon. Transanal endorectal pull-through was performed in 30 (35.7%) patients (group I), while 54 (64.3%) patients were operated by other (Soave, Duhamel or Swenson) procedures (group II). The age at operation, the incidence and severity of postoperative complications, the need for previous colostomy and the number of...
Pediatric Gastroesophageal Reflux Surgery – Indications and Frequency

Srpski arhiv za celokupno lekarstvo, 2014
Introduction. Intussusception is a common abdominal emergency in early childhood. It is idiopathi... more Introduction. Intussusception is a common abdominal emergency in early childhood. It is idiopathic in more than 90% of cases with incidence of 1.5-4 per 1,000 live births. The treatment of choice is nonoperative hydrostatic or air enema reduction. Objective. The aim of the study was to evaluate the influence of clinical presentation and symptom duration in non-operative treatment, considering the indications for delayed enema reduction and its efficacy. Methods. From the total number of 107 patients with intusussception, aged from 2 months to 14 years (median 9 months), 102 (95%) patients with ileo-colic intussusceptions were treated initially by ultrasound guided saline enema. Records were reviewed for patients with failed initial treatment and delayed repeated enemas or operative procedure. The predictor variable included duration of presenting symptoms. Results. Successful treatment by hydrostatic saline enemas had 58/102 (57%) patients. Success in reduction was greater if sympto...

European Journal of Pediatric Surgery, 2013
Aim Evaluation of the effectiveness of oral atropine versus surgical therapy for hypertrophic pyl... more Aim Evaluation of the effectiveness of oral atropine versus surgical therapy for hypertrophic pyloric stenosis (HPS). Methodology A total of 66 consecutive patients with HPS were treated at the University Children's Hospital between January 2006 and December 2011. The diagnosis was initially based on medical history and confirmed by ultrasonography (US). The patients were divided into two groups according to the treatment preferred by their parents. The conservatively treated group, consisting of 33 boys and 7 girls, mean age 22.25 days, was given water-soluble atropine sulfate therapy at an initial dose of 0.05 mg/kg/day divided into 8 single doses, and administered after stomach decompression, 20 minutes prior to feeding. If vomiting persisted, the daily dose was progressively increased up to 0.18 mg/kg. If vomiting did not stop and full oral feeding was not reestablished in a week, surgery was done. The second group of 26 patients, mean age 20.86 days, underwent an operative procedure, Ramstedt extramucosal pyloromyotomy after the initial resuscitation. US evaluation was performed on days 7, 14, and 21. The outcome of the treatment was tested by Yates modification of the χ2 test. Results In the group of patients treated with atropine sulfate, 10 (25%) failed to respond to therapy, therefore, 8 boys and 2 girls underwent surgical treatment between the fifth and seventh day following institution of therapy. The remaining patients who received atropine sulfate (75%) were discharged when vomiting ceased, between the sixth and eighth day. They continued to take oral medication for 4 to 6 weeks, and were followed up by an ultrasound examination. The operated patients were discharged between the third and fifth day after surgery. There was a significant statistical

Clinical Pharmacology & Therapeutics, 2012
state art nature publishing group Cystic fibrosis, also referred as mucoviscidosis, is a lifethre... more state art nature publishing group Cystic fibrosis, also referred as mucoviscidosis, is a lifethreatening autosomal recessive genetic disorder affecting multiple organs, most critically the respiratory and digestive systems. The prognosis for cystic fibrosis has significantly improved as a result of earlier diagnosis, better treatment, and expanded access to specialized care. Modern cystic fibrosis care incorporates a longitudinal strategy that includes early prenatal detection, management of disease manifestations during infancy and childhood, and chronic treatment in the adult. Decoding the pathogenesis of cystic fibrosis has advanced personalized treatment algorithms. Most notable is the realization that cystic fibrosis is a generalized exocrinopathy with reduced chloride ion transport across cell membranes as a consequence of a primary genetic disorder within the long arm of chromosome 7 encoding the transmembrane conductance regulating protein (CFTR). In healthy duct epithelia, chloride is transported by plasma membrane channels. Opening of chloride channels is mediated by an agonist-induced increase in cyclic adenosine monophosphate, followed by activation of protein kinase A, which phosphorylates channel proteins. 1 The impact of defective chloride transport differs in various tissues. In sweat gland ducts, it leads to decreased reabsorption of sodium chloride from the lumen, resulting in an increased concentration of sweat chloride, the basis for clinical diagnosis of cystic fibrosis. In other epithelia, especially the respiratory and intestinal epithelia, as well as in the biliary and pancreatic ducts, chloride channel defects result in loss or reduction of chloride secretion. Active sodium absorption is also increased, and these concomitant ionic changes increase water reabsorption from the lumen. As a consequence, dehydration of the mucus layer leads to viscid secretions, resulting in lumen obstruction and predisposing over time to recurrent infection, inflammation, fibrosis, and organ failure. The pronounced improvement in life expectancy for patients with cystic fibrosis, which is experienced across global health systems, particularly in developed countries, is a result of early diagnosis and improved symptomatic treatment based on control of airway infections, intestinal function, mobilization of secretions, reduction of inflammation, and improved nutrition. 2 Treating the fundamental defect underlying cystic fibrosis through a gene-modifying therapy offers the prospect of potential cures. In this regard, encouraging results from early clinical trials with mutation-correcting drug and gene therapy pave the way to more efficient management in the future. 3 Prenatal Diagnosis Cystic fibrosis is a hereditary, autosomal recessive disease, passed on from parents to offspring, with the highest prevalences of 1 in 3,000 Caucasian children of northern European descent and from North America and 1 in 2,300 in the Ashkenazi Jewish population. Other ethnic and racial groups are less commonly affected, reflected in the prevalences of 1 in 10,000 in the Latino American population and 1 in 15,000 in African Americans. The disease is uncommon in Africa and Asia, with reported frequencies ranging from 1 in 35,000 to 1 in 350,000. The earliest manifestation of cystic fibrosis may be associated with bowel lesions identified at prenatal ultrasonography, especially

European Pediatric Surgeons' Association Survey on the Use of Splenic Embolization in Blunt Splenic Trauma in Children
European Journal of Pediatric Surgery
Introduction This article assesses (1) access to splenic embolization (SE), (2) indications for S... more Introduction This article assesses (1) access to splenic embolization (SE), (2) indications for SE, and (3) post-embolization management in high-grade splenic trauma in children. Materials and Methods An online questionnaire was sent in 2021 to all members of European Pediatric Surgeons' Association. Results There were a total of 157 responses (50 countries, 83% academic hospitals). Among them, 68% have access to SE (SE) and 32% do not (nSE). For a hemodynamic stable patient with high-grade isolated splenic trauma without contrast extravasation (CE) on computed tomography (CT) scan, 99% SE and 95% nSE respondents use nonoperative management (NOM). In cases with CE, NOM decreases to 50% (p = 0.01) and 51% (p = 0.007) in SE and nSE centers, respectively. SE respondents report a significant reduction of NOM in stable patients with an associated spine injury requiring urgent surgery in prone position, both without and with CE (90 and 28%, respectively). For these respondents, in sta...

Vojnosanitetski pregled, 2019
Introduction/Aim. Infantile hypertrophic pyloric stenosis (IHPS) is the most common cause of surg... more Introduction/Aim. Infantile hypertrophic pyloric stenosis (IHPS) is the most common cause of surgery in the newborn and young infant. Conservative treatment of IHPS is of a great importance because it saves a newborn from stress caused by surgery and general anesthesia. This study evaluates the impact of various oral administration regimens of atropine on its efficacy in treating IHPS. Methods. The study included 45 patients with IHPS, conservatively treated by atropine sulfate in the period from 2006-2016. Clinical examination, laboratory analysis and ultrasonography were performed for all patients on admission. We analyzed the efficacy of treatment, with different oral dosage regimens and definition of potential predictive factors of the negative outcome. Evaluation was statistically analyzed by the method of multivariate logistic regression model. Results. Group of patients, conservatively treated, included 45 patients, of whom 36 (80%, p=0,0008) were successfully cured, without need for surgery and without complications. It has been shown that in terms of sex prevalence, age, birth weight, body weight on admission, duration of symptoms, pyloric muscle thickness and length, there is no statistically significant individual effect on the success of atropine treatment. Patients who received progressively increased dose of atropine have an 18 times higher risk of surgery, patients who have hypochloremic alkalosis (HCA) have a 15 times higher risk, while others, who have more than 5 vomiting within the first three days of therapy are 9 times more likely to be surgically treated. Conclusion. High success rate and no side effects represent an orally administered atropine treatment as a valid alternative indication for non-operative management of IHPS. Administration of initially high doses has been shown to be more effective in relation to gradually increased oral doses of atropine sulfate. HCA and continued vomiting are considered as potential predictive factors of negative outcome of atropine treatment.

Serbian Journal of Experimental and Clinical Research, 2016
Acute inflammation of the appendix in childhood usually requires an appendectomy. Surgical method... more Acute inflammation of the appendix in childhood usually requires an appendectomy. Surgical methods are open appendectomy (OA) and laparoscopic appendectomy (LA). Both have the same goal of removing the appendix.Data collected from the medical records of children who underwent hospitalization and operation for acute appendicitis have been retrospectively analysed and statistically processed. The patients underwent surgery in 2010 at University Children’s Hospital in Belgrade, and the methods that were used were open appendectomy (OA) and laparoscopic appendectomy (LA). The analysed data refer to gender, age, length of hospital stay, surgery duration, use of pain management therapy, and antibiotic therapy, complications during surgery, complications after surgery, re-hospitalizations, and reoperations.A total of 218 children underwent an appendectomy operation, of which 158 (72.5%) underwent OA and 60 (27.5%) underwent LA. The average age of patients who had OA was 11.44 years, and 10...
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Papers by Sanja SINDJIC-ANTUNOVIC