Sherif Emil

A Recurrent PDGFRB Mutation Causes Familial Infantile Myofibromatosis

Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor β (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-β promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-β as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-β in aggressive life-threatening familial forms of the disease.

Cue-evoked arousal in cocaine users: a study of variance and predictive value

Thirty-six cocaine abusers in treatment and 16 non-using controls were exposed to visual cocaine cues; measurements included changes in skin conductance and a rating of psychological arousal (persisting cocaine thoughts and images during the 24 h following the experiment). The GSI score of the HSCL-58 was used as an indicator of psychological distress. Probands showed arousal responses significantly higher than the controls. Skin conductance readings correlated positively with HSCL-58 scores and with severity of craving in the week prior to the trial. Unexpectedly, they correlated negatively with duration of cocaine use and did not vary as a function of the severity of cocaine addiction or the duration of cocaine abstinence prior to the test. Neither cocaine addiction measurements nor arousal responses were found to predict cessation of use (a minimum of 3 months of sustained abstinence) 1 year after the test.

Contemporary 2-year outcomes of complex gastroschisis

PURPOSE Outcomes of gastroschisis are influenced by associated intestinal complications. We present a detailed analysis of complex gastroschisis. METHODS A retrospective study of all patients with gastroschisis treated at 2 university neonatal intensive care units between January 1, 2001, and March 31, 2007, was performed. RESULTS Of 83 patients, 19 (23%) had complex gastroschisis, including atresias (68%), gangrene (37%), closing gastroschisis (32%), perforation (21%), strictures (21%), and volvulus (11%). Prenatal ultrasound did not predict complications. Fifty-three percent underwent primary closure. Duration of mechanical ventilation and total parenteral nutrition (TPN) was 14.4 ± 1.9 days and 90.7 ± 9.0 days, respectively. Enteral feeds started at 35.9 ± 4.6 days. Hospital stay was 104.4 ± 9.6 days. Patients underwent a median of 3 abdominal procedures (range, 2-5) before discharge. Ninety-five percent survived to discharge; 33% and 67% were discharged on TPN and gastrostomy feeds, respectively. Two-year survival was 89%, with 82% on full oral feeding, 12% on a combination of oral and gastrostomy feeding, and 1 patient (who received a liver/bowel transplant) on a combination of enteral and parenteral nutrition. CONCLUSIONS Complex gastroschisis continues to produce significant morbidity. However, most of the patients are TPN free by 2 years of age.

Vacuum-assisted closure for complicated neonatal abdominal wounds

BACKGROUND Neonatal experience in vacuum-assisted closure (VAC) for complex abdominal wounds remains scant. METHODS A neonatal VAC protocol was instituted in 2004. The medical records of patients treated with this protocol for the ensuing 3 years were retrospectively reviewed. Continuous data are reported as mean +/- SD (range). RESULTS Ten VAC applications occurred in 8 neonates for a 3-year period. Gestational age and age at VAC application were 30 +/- 6.9 (24-40) weeks and 84.5 +/- 51 (21-165) days, respectively. Birth weight and weight at VAC application were 1495 +/- 1118 (615-3415) g and 3515 +/- 2118 (989-7965) g, respectively. All wound complications occurred after laparotomies (7 elective, 3 emergent). Three wounds included intestinal stomas, and 3 included enterocutaneous fistulae. Average wound area at VAC initiation was 13.6 +/- 6.0 (8.5-25) cm(2). Duration of VAC use was 19.1 +/- 15.3 (7-60) days. Vacuum-assisted closure resulted in complete wound closure in all cases and did not result in any local or systemic complications. Five patients (63%) survived to discharge. CONCLUSIONS Vacuum-assisted closure for complicated abdominal wounds is safe and successful in neonates of any gestational age and birth weight. It provides effective wound management, even in the presence of stomas or enterocutaneous fistulae.

A comparison of techniques for laparoscopic gastrostomy placement in children

BACKGROUND The insertion of gastrostomy tube (GT) for children is typically accomplished using a minimally invasive approach. There is considerable variability in the technical details of this operation, depending on how much of the procedure is performed intracorporeal. The purpose of this study is to compare the outcomes and resource utilization of two differing techniques for laparoscopic GT insertion in the pediatric population. MATERIALS AND METHODS A single-center retrospective review of all patients who underwent a laparoscopic GT insertion from 2001-2011 was conducted and analyzed based on technique of insertion. This was laparoscopy plus either an intracorporeal Seldinger technique, or an extracorporeal insertion approach, (mini-open technique; [MOT]). Outcomes investigated included short-term complications within the first mo (dislodgement, infection), long-term complications (infection, need for revision, dislodgement), and measures of resource utilization (operative time, material cost, and GT-related hospital visits). RESULTS A total of 129 insertions were performed; 87 (67.4%) done using the Seldinger technique, and 42 underwent MOT. Overall, complication rates did not differ between the two groups. Of all patients who underwent a GT placement, 38% were treated for granulation tissue, 27.1% experienced dislodgement, and 23.3% were reported to have a GT-related infection. The MOT approach was associated with a 29% reduction in disposable operating room costs and a 57% reduction in emergency department visits (P < 0.05). CONCLUSIONS Pediatric patients undergoing laparoscopic gastrostomy tube insertion via the Seldinger or MOT method have similar morbidity risks, although MOT was associated with less overall resource utilization in this study.

Gangrenous appendicitis in children: a prospective evaluation of definition, bacteriology, histopathology, and outcomes

INTRODUCTION The definition and treatment of gangrenous appendicitis are not agreed upon. We performed a prospective study in children to evaluate an objective definition of gangrenous appendicitis, as well as associated bacteriology, histopathology, and outcomes. METHODS Five staff pediatric surgeons prospectively enrolled patients in the study at the time of appendectomy if the following five criteria were met: gray or black discoloration of the appendiceal wall; absence of fecalith outside the appendix; absence of visible hole in the appendix; absence of gross purulence or fibrinous exudate remote from the appendix; and absence of intraoperative appendiceal leak. Peritoneal fluid was cultured, and a standard histopathologic review was undertaken. Persistence of fever (>37.5°C) and ileus was documented daily. Patients were continued postoperatively on ampicillin, gentamicin, and metronidazole until they tolerated diet, manifested a 24-h afebrile period, and had a normal leukocyte count. Hospital stay, readmissions, and infectious complications were recorded. The study took place over a 12-mo period. RESULTS Thirty-eight patients were enrolled, representing 17% of all patients with appendicitis treated during the year. Average age was 10.8 ± 3.5 y. Peritoneal cultures were positive in 53% of cases. Gangrene was documented histologically in 61% of specimens. Hospital stay was 3.2 ± 1.1 d. There were no postoperative infectious complications or readmissions related to the disease. Neither culture results nor histologic gangrene had a statistically significant effect on hospital stay. CONCLUSIONS An objective definition of gangrenous appendicitis is reproducible and has good histopathologic association. Recovery from gangrenous appendicitis is not influenced by culture or pathology results, and postoperative complications are rare. Limiting postoperative antibiotics to 24 h in gangrenous appendicitis may significantly decrease the cost of treatment without increasing morbidity.

Gastroschisis outcomes in North America: a comparison of Canada and the United States

BACKGROUND Care of infants with gastroschisis is centralized in Canada and noncentralized in the United States. We conducted an outcomes comparison between the two countries and analyzed the determinants of such outcomes. METHODS Inpatient mortality and hospital stay of gastroschisis patients from the Canadian Pediatric Surgery Network prospective clinical database for the period 2005-2013 were compared with those from the US Kids Inpatient Database for the period 2003-2012. Potential outcome determinants were analyzed using univariate and multivariate analyses. RESULTS A comparison was made between 695 Canadian patients and 5216 American patients. Complex gastroschisis was found in 16.0% and 13.7% of patients in Canada and the US, respectively; P=0.11. Canada had less premature births, more normal birth weight (BW) infants, less cesarean section deliveries, and more inborn patients compared to the US. For simple gastroschisis, Canadian mortality was lower (1.4% vs. 3.4%; P=.008) and hospital stay was longer (45±38 vs. 41±32days; P=.04). US mortality correlated strongly with low BW (P=.002) and marginally with cesarean section delivery (P=.08). A longer Canadian hospital stay was associated with lower gestational age (P=0.01) and western region (P=0.04), while a longer American hospital stay was associated with medium neonatal intensive care unit gastroschisis volume (P=.03), low socioeconomic status (P=.06), low BW (P=0.06), and public insurance (P=0.07). Outcomes for complex gastroschisis did not differ between Canada and the US. CONCLUSIONS Mortality for simple gastroschisis is higher in the US than in Canada, whereas no outcome differences exist for complex gastroschisis. Outcome determinants are different between the 2 countries.

Laparoscopic Treatment of Isolated Salpingeal Torsion in Children: Case Series and a 20-Year Review of the Literature

BACKGROUND Isolated torsion of the Fallopian tube, without ovarian torsion, is a rare cause of lower abdominal pain. We report our experience with 4 recent cases, along with data from a 20-year review of the pediatric literature. SUBJECTS AND METHODS The records of 4 cases encountered during a 3-year period were reviewed. A literature review was completed by searching Medline, Medline in Process, Embase, Current Contents, and BIOSIS from 1990 to 2010. RESULTS All 4 patients were diagnosed on laparoscopy. Laparoscopic salpingectomy was performed in 3 cases and laparoscopic detorsion in 1. All three resected specimens revealed hemorrhage and gangrene of the salpinx, with an associated cyst in one. The pediatric literature review, including our report, revealed 33 case reports and case series with 45 patients. Fifty-six percent of cases represented primary torsion, and 44% were secondary to underlying tubal pathology. Thirty percent of girls were premenarchal. The mean age at presentation and symptom duration were 13.2±2.1 years and 5.8±12.5 days, respectively. Fever and leukocytosis were present in 27% and 63%, respectively. Ultrasound, computed tomography scan, and magnetic resonance imaging showed a sensitivity of 22% (8/36), 14% (1/7), and 40% (2/5), respectively. A correct preoperative diagnosis was considered in only 13%. Eighty-eight percent of cases were treated by salpingectomy, and 12% were treated by tubal detorsion. Long-term outcomes of detorsion were not reported. CONCLUSIONS Isolated salpingeal torsion in girls is rarely diagnosed preoperatively, regardless of imaging technique. Laparoscopy is the intervention of choice for definitive diagnosis and management. Salpingectomy is the most frequent treatment. Detorsion without resection may be considered for selected cases, but the long-term outcomes of this approach are unknown.

Cervical esophageal duplication cyst: case report and review of the literature ☆

Cervical esophageal duplication cysts are rare congenital anomalies that can be successfully managed surgically. These anomalies are rare causes of upper airway obstruction. We present here a case of a cervical esophageal duplication cyst in an infant, along with a review of the literature concerning this anomaly.

Pediatric laparoscopic appendectomy: a population-based study of trends, associations, and outcomes

PURPOSE We performed a population-based study to analyze the trends, associations, and outcomes of laparoscopic appendectomy (LA) in the Canadian universal health care setting. METHODS Children younger than 18years coded for urgent appendectomy in the discharge abstract database of the Canadian Institute of Health Information during 2004-2010 were analyzed. The Cochran-Armitage test, logistic regression, and quintile regression were used to perform the necessary analyses. RESULTS 41,405 children were studied. LA incidence steadily increased from 28.8% to 66.4%, p<.0001. Conversion rates significantly decreased, while LA for perforated appendicitis significantly increased. LA occurred significantly less in younger patients [OR 0.24 (<5years), OR 0.45 (6-11 years)], males [OR 0.79], and operations by a general surgeon [OR 0.33]. Rural domicile, socioeconomic status, and hospital type had no effect. LA decreased hospital stay for simple appendicitis by one day beginning in 2006, and by variable durations for perforated appendicitis throughout the study period. CONCLUSIONS The incidence of LA in Canada has more than doubled. Older children, females, and patients treated by pediatric surgeons are more likely to receive LA, while domicile, socioeconomic status, and hospital type have no effect. LA reduced hospital stay for both simple and perforated appendicitis.