The genetic factors contributing to the risk of cleft lip-cleft palate and their clinical utility.

Cleft lip and cleft palate (CL/P) are among the most common congenital malformations in neonates and have syndromic or nonsyndromic forms. Nonsyndromic forms of malformation are being reported to be associated with chromosomal DNA modification by teratogenic exposure and to complex genetic contributions of multiple genes. Syndromic forms are shown to be related to chromosomal aberrations or monogenic diseases. There is a growing body of data illustrating the association of several genes with risk of developing this malformation, including genetic defects in T-box transcription factor-22 (TBX22), interferon regulatory factor-6 (IRF6), and poliovirus receptor-like-1 (PVRL1), responsible for X-linked cleft palate, cleft lip/palate-ectodermal dysplasia syndrome, and Van der Woude and popliteal pterygium syndromes, respectively. Genetic variants in MTR, PCYT1A, ASS1, SLC 25A13, GSTM1, GSTT1, SUMO1 BHMT1, and BHMT2 are being reported to be linked with CL/P risk. The etiology of nonsyndromic CLP is still remained to be unknown, although mutations in candidate genes have been found. Here, we provide an overview about the potential variants to be associated with CL/P for identification of the relative risk of CLP with respect to the basis of genetic background and environmental factors (e.g., dietary factors, alcohol use).

The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of Circulating Tumor Cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer.

The genetic factors contributing to hypospadias and their clinical utility in its diagnosis.

Hypospadias is among the most common congenital malformations in male neonates. It results from abnormal penile and urethral development, but is a multifactorial disorder that is highly heterogeneous, with several genetic and environmental determinants. Monogenic and chromosomal abnormalities are present in approximately 30% of cases, although the genetic factors contributing to hypospadias remain unknown in 70% of cases. While defects in androgen synthesis can lead to this malformation, mutational analyses have shown several genes, such as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins, homeobox genes, and the Wnt family, are involved in the normal development of male external genitalia. Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias. Here we review the recent advances in this field and discuss the potential genes that could determine the risk of hypospadias.

The genetic factors contributing to the development of Wilm's tumor and their clinical utility in its diagnosis and prognosis.

Mutations in the Wilm's tumor 1 (WT1) gene are associated with a wide spectrum of renal manifestations, ultimately leading to end-stage kidney failure. There is an inadequate understanding of the molecular functions of WT1 in renal development, and this has limited the potential for therapeutic interventions in WT1-related diseases. In this review, we discuss the existing data on the genetic and epigenetic abnormalities that have been described in WTs and their potential utility as biomarkers for risk stratification, prediction and prognosis in patients with WTs.

Genetic Background of Hirschsprung Disease: A Bridge Between Basic Science and Clinical Application.

Hirschsprung's disease (HSCR) is a congenital disorder, defined by partial or complete loss of the neuronal ganglion cells in the intestinal tract, which is caused by the failure of neural crest cells to migrate completely during intestinal development during fetal life. HSCR has a multifactorial etiology, and genetic factors play a key role in its pathogenesis; these include mutations within several gene loci. These have been identified by screening candidate genes, or by conducting genome wide association (GWAS) studies. However, only a small portion of them have been proposed as major genetic risk factors for the HSCR. In this review, we focus on those genes that have been identified as either low penetrant or high penetrant variants that determine the risk of Hirschsprung's disease. J. Cell. Biochem. 119: 28-33, 2018. © 2017 Wiley Periodicals, Inc.

The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials.

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) is suggested to be associated with resistance to alkylating agents such as Temozolomide which is being used in treatment of patients with glioblastoma (GBM). Therefore, we evaluated the associations between MGMT promoter methylation and prognosis of patients with glioblastoma (GBM). Data were extracted from publications in Embase, PubMed, and the Cochrane Library. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained and 4,097 subjects were enrolled. Data from 34 studies showed that MGMT methylated patients had better OS, compared to GBM unmethylated patients (pooled HRs, 0.494; 95%CI 0.412-0.591; p = 0.001). Meta-analysis of 10 eligible studies reporting on PFS, demonstrated that MGMT promoter methylation was not significantly associated with better PFS (pooled HRs, 0.653; 95%CI 0.414-1.030; p = 0.067). GBM patients with MGMT methylation were associated with longer overall survival, although this effect was not detected for PFS. Moreover, we performed further analysis in patients underwent a comprehensive imaging evaluation. This data showed a significant association with better OS and PFS, although further studies are warranted to assess the value of emerging marker in prospective setting in patients with glioblastoma as a risk stratification biomarker in clinical management of the patients.

Controlled vs Spontaneous Ventilation for Bronchoscopy in Children with Tracheobronchial Foreign Body.

INTRODUCTION: Tracheobronchial foreign body aspiration is a common life-threatening condition in children. There are controversies in the management of this condition, including the type of ventilation during bronchoscopy. This study aims to compare anesthesia with controlled ventilation versus spontaneous ventilation in rigid bronchoscopy in children with foreign body aspiration. MATERIALS AND METHODS: Patients who were candidates for rigid bronchoscopy due to foreign body aspiration were randomly assigned to either anesthesia with spontaneous ventilation or controlled ventilation. End tidal CO2 (ETCO2), electrocardiogram (ECG), heart rate (HR), oxygen saturation (SpO2), non-invasive blood pressure (NIBP) and complications and accidents during the surgery and recovery were recorded for each patient. Surgeon comfort during the procedure was also evaluated for each patient. A 20% change in HR or NIBP was considered significant. SpO2 values under 90% are considered desaturation. RESULTS: Fifty-one patients (31 male and 20 female) entered the study. The mean age was 26.76 months, ranging from 6 to 100 months. Choking and cough were present in 94% and 96.1% of the patients, respectively. Nuts were the most common foreign body (76.9%). The controlled ventilation group had significantly fewer complications, and surgeon comfort was significantly higher in this group. Oxygen desaturation was significantly more prevalent in the spontaneous ventilation group during laryngoscopy and bronchoscopy (P<0.001). CONCLUSION: Controlled ventilation has the potential to be used as an effective alternative option in anesthesia for patients with suspected foreign body aspiration.

Thoracoscopic Esophageal Atresia with Tracheoesophageal Fistula Repair: The First Iranian Group Report, Passing the Learning Curve.

BACKGROUND: Thoracoscopic treatment of esophageal atresia and tracheoesophageal fistula (EA+TEF) is accepted as a superior technique at least in cosmetic point of view but it is considered as an advance endoscopic procedure that needs a learning curve to be performed perfectly. This is the first report of Iranian group pediatric surgeons in thoracoscopic approach to EA. METHODS AND MATERIALS: Since 2010, twenty four cases with EA+TEF underwent thoracoscopic approach in Sarvar Children Hospital (Mashhad -Iran). During the first 6 months, thoracoscopic approach to 6 cases of EA+TEF was converted to open procedure because of technical and instrumental problems. The first case of successful thoracoscopic EA repair was accomplished in 2010 and since then, 10 cases of EA+ TEF among 18 patients were treated successfully with thoracoscopic approach RESULTS: Overall conversion rate was 58.3% but conversion rate after the primary learning curve period, was 35.7%. The main conversion causes include difficulties in esophageal anastomosis, limited exposure and deteriorating the patient's condition. Anastomotic leak and stenosis were observed in 20% and 40% respectively. Overall mortality rate was 4.2%. CONCLUSION: Thoracoscopic repair of esophageal atresia seems feasible and safe with considerable superiorities to the conventional method although acceptable results needs a prolonged learning curve and advanced endoscopic surgical skill. Clear judgment about the best surgical intervention for EA according to all cosmetic and functional outcomes needs further studies.

"Tie over ring" sutureless compression based gastrointestinal anastomotic method: experimental rat model.

INTRODUCTION: Giving the ever-rising trend of pediatric minimally invasive surgery besides early neonatal surgical interventions, intestinal anastomosis turns out to be a time consuming stage due to several anatomical as well as technical difficulties. A perfect bowel anastomosis method should be easy, rapid, safe and reliable in creation of bowel continuity with minimal tissue damage. In this light, sutureless anastomotic methods have been introduced, using compression based anastomosis with biofragmentable rings or powerful magnets. Accordingly, this experimental animal model study has evaluated the result of an easy, rapid intestinal sutureless anastomotic technique via simple tying over an intraluminal ring, in comparison with conventional handsewn bowel anastomosis. METHODOLOGY: Thirty Wistar-Albino male rats were enrolled and small bowel was transected via a midline laparotomy. A grooved plastic ring was inserted into the ileal lumen and both intestinal cutting ends were fixed over the ring with a simple tie in the first group. On the other hand, enteroenterostomy was performed by the conventional method of handsewn anastomosis in the second group. After 14 days, rats were sacrificed to evaluate for intraperitoneal adhesion and abscess formation in addition to other evidences of anastomotic leakage. Furthermore, the anastomotic site integrity, tensile strength and healing stage were assessed microscopically. RESULTS: The mean operative time and intraoperative bleeding in the tie over ring group were significantly less than those in the handsewn anastomosis group. Anastomotic stricture was more common in the conventional anastomosis group while the anastomotic tensile strength was significantly higher in the tie over ring group. Histopathological healing parameters and final healing score were almost similar in both groups but mean inflammatory cell infiltration in handsewn anastomosis was significantly higher. CONCLUSION: "Tie over ring" is a simple method of anastomosis that is feasible, fast, safe and functionally effective for bowel reconstruction in animal models that could be reconsidered in human bowel anastomosis.

Thoracoscopic esophageal atresia repair made easy. An applicable trick.

Thoracoscopic repair of esophageal atresia is becoming more popular but technical difficulties in handsewn anastomosis still remain challenging. This article presents an easy and applicable maneuver by passing the trans-esophageal tube before starting to suture in order to minimize the gap, reduce the tension over primary sutures and provide a better visualization of posterolateral parts of the anastomosis in thoracoscopic esophageal atresia repair. Using this maneuver makes tying easier and minimizes grasping and crushing damages to the anastomotic site.

Spontaneous perforation of common bile duct in a pediatric patient: application of hepatobiliary scintigraphy.

We report a case of spontaneous biliary perforation in a 21-month old female pediatric patient with the presenting symptoms of abdominal distension, jaundice, and umbilical hernia. Hepatobiliary scintigraphy showed tracer accumulation in the peritoneal cavity. Preliminary diagnosis of spontaneous biliary perforation was confirmed during surgery. After surgical repair of the biliary leakage, the patient recovered fully. This case shows the importance of hepatobiliary scintigraphy in patients suspicious for this condition.

Pediatric clear cell sarcoma of the kidney with atriocaval thrombus.

Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for almost 3 % of pediatric renal tumors. Cavoatrial tumor thrombosis is very rare and because of poor response to chemotherapy, invasive surgical interventions such as open heart surgery may be indicated. A 6-year-old girl with CCSK of right kidney was treated with neoadjuvant chemotherapy. According to poor chemosensitivity, surgical intervention was planned. Right atriotomy was done, but intra-atrial part of tumor was very firm and unsuctionable; so the procedure was completed by laparotomy and en bloc resection of tumoral kidney and its cavoatrial extension through a limited venotomy on inferior vena cava. Although radical resection of CCSK with intracaval involvement should be considered as a multidisciplinary approach and intensive care and supports should be provided, atriocaval tumor in growth in CCSK is firm, non friable and non-adherent, and tumor en bloc resection may be possible through a limited venotomy via primary abdominal approach.