Mikael Petrosyan

Current concepts regarding the pathogenesis of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a devastating disease that predominantly affects premature neonates. The mortality associated with NEC has not changed appreciably over the past several decades. The underlying etiology of NEC remains elusive, although bacterial colonization of the gut, formula feeding, and perinatal stress have been implicated as putative risk factors. The disease is characterized by massive epithelial destruction, which results in gut barrier failure. The exact molecular and cellular mechanisms involved in this complex disease are poorly understood. Recent studies have provided significant insight into our understanding of the pathogenesis of NEC. Endogenous mediators such as prostanoids, cyclooxygenases, and nitric oxide may play a role in the development of gut barrier failure. Understanding the structural architecture of the gut barrier and the cellular mechanisms that are responsible for gut epithelial damage could lead to the development of novel diagnostic, prophylactic and therapeutic strategies in NEC.

Disparities in the delivery of pediatric trauma care.

BACKGROUND Trauma is the leading cause of morbidity and mortality in children. During the last few decades, trauma systems have evolved to improve the care of the injured with an ultimate goal of saving lives. As a result, pediatric trauma centers (PTC) have been established to optimize outcomes for injured children. We sought to determine whether injured children treated at PTC or adult trauma centers (ATC) with added qualifications to treat injured children receive better trauma care than those treated at other hospitals or trauma centers. METHODS We reviewed more than 60 published studies on pediatric trauma outcomes. The studies included registry analysis: single and multihospital experience; abdominal, head and neck, and thoracic trauma; as well as functional outcomes. RESULTS The data show that most injured children are not treated at PTC due to the geographically limited distribution of such specialized care, lack of pediatric surgeons, and other specialists. These limitations create persistent disparities in outcomes for injured children depending on where they are treated. Some of the larger database analyses suggest lower mortality rate, better outcome for nonoperative treatment of blunt abdominal injuries, and improved overall functional outcome for those children treated at PTC. However, others fail to demonstrate differences for children treated at ATC or ATC with added qualifications. CONCLUSION Although this analysis does not provide a definitive answer to the question as to which type of trauma center provides better care for injured pediatric patients, it identifies current gaps and disparities in the care of injured children that can be remedied through education and training.

Psoas abscess rarely requires surgical intervention.

BACKGROUND Surgeons are increasingly encountering psoas abscesses. METHODS We performed a review of 41 adults diagnosed and treated for psoas abscess at a county hospital. Treatment modalities and outcomes were evaluated to develop a contemporary algorithm. RESULTS Eighteen patients had a primary psoas abscess, and 23 had a secondary psoas abscess. Patient characteristics were similar in both groups. Intravenous drug abuse was the leading cause of primary abscesses. Secondary abscesses developed most commonly after abdominal surgery. Treatment was via open drainage (3%), computed tomography-guided percutaneous drainage (63%), or antibiotics alone (34%). Four recurrences occurred in the percutaneous group. Statistical analysis showed that the median size of psoas abscesses in the percutaneous group was significantly larger than in the antibiotics group (6 vs 2 cm; P < .001). The mortality rate was 3%. CONCLUSIONS Initial management of psoas abscesses should be nonsurgical (90% success). Small abscesses may be treated with antibiotics alone, and surgery can be reserved for occasional complicated recurrences.

Lactobacillus bulgaricus Prevents Intestinal Epithelial Cell Injury Caused by Enterobacter sakazakii-Induced Nitric Oxide both In Vitro and in the Newborn Rat Model of Necrotizing Enterocolitis

ABSTRACT Enterobacter sakazakii is an emerging pathogen that has been associated with outbreaks of necrotizing enterocolitis (NEC) as well as infant sepsis and meningitis. Our previous studies demonstrated that E. sakazakii induces NEC in a newborn rat model by inducing enterocyte apoptosis. However, the mechanisms responsible for enterocyte apoptosis are not known. Here we demonstrate that E. sakazakii induces significant production of nitric oxide (NO) in rat intestinal epithelial cells (IEC-6) upon infection. The elevated production of NO, which is due to increased expression of inducible NO synthase, is responsible for apoptosis of IEC-6 cells. Notably, pretreatment of IEC-6 cells with Lactobacillus bulgaricus (ATCC 12278) attenuated the upregulation of NO production and thereby protected the cells from E. sakazakii-induced apoptosis. Furthermore, pretreatment with L. bulgaricus promoted the integrity of enterocytes both in vitro and in the infant rat model of NEC, even after challenge with E. sakazakii. Infection of IEC-6 cells with E. sakazakii upregulated several genes related to apoptosis, cytokine production, and various signaling pathways, as demonstrated by rat gene array analysis, and this upregulation was subdued by pretreatment with L. bulgaricus. In agreement with these data, L. bulgaricus pretreatment protected newborn rats infected with E. sakazakii from developing NEC, resulting in improved survival.

Role of the Host Defense System and Intestinal Microbial Flora in the Pathogenesis of Necrotizing Enterocolitis

BACKGROUND Necrotizing enterocolitis (NEC) is a devastating disease that affects primarily the intestine of premature infants. Despite recent advances in neonatology, NEC remains a major cause of morbidity and mortality in neonates. Neonatal mucosal defenses and adherence of bacterial pathogens may play an important role in the pathogenesis of NEC. METHODS Review and synthesis of pertinent literature. RESULTS Putative factors that have been implicated in the pathogenesis of NEC include abnormal patterns of gut colonization by bacteria, immaturity of the host immune system and mucosal defense mechanisms, intestinal ischemia, formula feeding, and loss of intestinal epithelial barrier integrity. CONCLUSION Host defenses and intestinal microbial ecology are believed to play important roles in the pathogenesis of NEC. Commensal bacteria and probiotic therapy may be of therapeutic utility in the maintenance of the gut epithelial barrier.

Childhood achalasia: A comprehensive review of disease, diagnosis and therapeutic management

Achalasia is an esophageal motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation and is rare in children. The most common symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive diagnosis is made with barium swallow study and esophageal manometry. In adults, endoscopic biopsy is recommended to exclude malignancy however; it is not as often indicated in children. Medical management often fails resulting in recurrent symptoms and the ultimate definitive treatment is surgical. Laparoscopic Heller myotomy with or without an anti-reflux procedure is the treatment of choice and has become standard of care for children with achalasia. Peroral endoscopic myotomy is a novel therapy utilized with increasing frequency for achalasia treatment in adults. More experience is needed to determine the safety, efficacy, and feasibility of peroral endoscopic myotomy in children.

Necrotizing enterocolitis--bench to bedside: novel and emerging strategies.

Necrotizing enterocolitis (NEC) is a devastating illness that predominantly affects premature neonates. The mortality associated with this disease has changed very little during the last two decades. Neonates with NEC fall into two categories: those who respond to medical management alone and those who require surgical treatment. The disease distribution may be focal, multifocal, or panintestinal. Surgical treatment should therefore be based on disease presentation. Recent studies have added significant insight into our understanding of the pathogenesis of NEC. Several groups have shown that upregulation of nitric oxide plays an integral role in the development of epithelial injury in NEC. As a result, some treatment strategies have been aimed at abrogating the toxic effects of nitric oxide. In addition, several investigators have reported the cytoprotective effect of epidermal growth factor, which is found in high levels in breast milk, on the intestinal epithelium. Thus, fortification of infant formula with specific growth factors could soon become a preferred strategy to accelerate intestinal maturation in the premature neonate to prevent the development of NEC. One of the most devastating complications of NEC is the development of short bowel syndrome (SBS). The current treatment of SBS involves intestinal lengthening procedures or bowel transplantation. A novel emerging method for treating SBS involves the use of tissue-engineered intestine. In laboratory animals, tissue-engineered small intestine has been shown to be successful in treating intestinal failure. This article examines recent data regarding surgical treatment options for NEC as well as emerging treatment modalities.

Laparoscopic Choledochal Cyst Excision: Lessons Learned in Our Experience

BACKGROUND Choledochal cyst (CDC) is a rare biliary disorder. Surgical treatment consists of CDC excision and biliary-enteric reconstruction. Recently, some institutions have reported successful CDC excision by using minimally invasive techniques. In this study, we report our experience with the laparoscopic management of CDC, with a focus on key operative maneuvers that enhance the likelihood of successful excision. METHODS Following institutional review board approval, we performed a retrospective review of patients who underwent the laparoscopic excision of CDC and Roux-en-Y hepaticojejunostomy. Between October 2003 and November 2007, we performed laparoscopic CDC excision in 9 patients (8 female and 1 male). Median age was 4 years (range, 8 months to 16 years). There were 7 type I and 2 type IV cysts, according to Todanis classification. Average cyst size was 4.4 cm (range, 1.3-8.5). The procedures were performed by utilizing four or five trochars. RESULTS Six of 9 children presented with preoperative pancreatitis, 1 with abdominal pain, 1 with jaundice, and 1 was found incidentally. Three patients required the conversion to laparotomy due to dense adhesions, secondary to pancreatitis. Six patients underwent successful laparoscopic procedures, 5 had complete cyst excisions, and 1 underwent a proximal excision with distal mucosectomy. Of the 3 patients who required conversion, 2 underwent complete excisions; the other underwent a proximal excision, distal mucosectomy. There were no intraoperative complications. One patient had a postoperative bile leak that required an open hepaticojejunostomy revision. Eight patients had an uneventful recovery. Oral feedings were resumed within an average of 3.4 days (range, 2-9). Average time to discharge was 6.1 days (range, 5-12). Average follow-up time was 18 months (range, 4-48). No further laboratory abnormalities were detected in any of the patients. CONCLUSIONS Laparoscopic resection of CDC and Roux-en-Y hepaticojejunostomy in children is an excellent treatment option. Preoperative pancreatitis may cause increased technical difficulty, necessitating a conversion. Proximal excision with distal mucosectomy

Prediction of Patients with Acute Cholecystitis Requiring Emergent Cholecystectomy: A Simple Score

The objective was to develop a score, to stratify patients with acute cholecystitis into high, intermediate, or low probability of gangrenous cholecystitis. The probability of gangrenous cholecystitis (score) was derived from a logistic regression of a clinical and pathological review of 245 patients undergoing urgent cholecystectomy. Sixty-eight patients had gangrenous inflammation, 132 acute, and 45 no inflammation. The score comprised of: age > 45 years (1 point), heart rate > 90 beats/min (1 point), male (2 points), Leucocytosis > 13,000/mm3 (1.5 points), and ultrasound gallbladder wall thickness > 4.5 mm (1 point). The prevalence of gangrenous cholecystitis was 13% in the low-probability (0–2 points), 33% in the intermediate-probability (2–4.5 points), and 87% in the high probability category (>4.5 points). A cutoff score of 2 identified 31 (69%) patients with no acute inflammation (PPV 90%). This scoring system can prioritize patients for emergent cholecystectomy based on their expected pathology.

CT Scan in Patients with Suspected Appendicitis: Clinical Implications for the Acute Care Surgeon

Objective: To determine the influence of computed tomography (CT) scans on diagnosis and management of patients with suspected appendicitis. Methods: Retrospective 2-year review of 1,630 patients with suspected appendicitis, categorized into three groups based on the likelihood (Alvarado scores) of having appendicitis. Group 1: low likelihood (Alvarado score ≤4); group 2: intermediate likelihood (Alvarado scores 5–7), and group 3: high likelihood (Alvarado score ≧ 8). CT scan utilization, hospital course, and final pathology were retrospectively reviewed. Results: More patients received a CT scan in 2006 as compared with 2005 (60 vs. 52%; p = 0.001). The overall appendectomy rate was similar between the 2 years (57% in 2005 vs. 57% in 2006; p = 0.995). The overall appendectomy rate in patients with a CT was significantly higher as compared with those without (60 vs. 53%; p = 0.002). The appendectomy rate in patients with Alvarado scores ≤4 and no CT scan was significantly lower than in those with a CT scan (12 vs. 48%; p < 0.0001). The overall negative appendectomy rate in patients with a CT scan was similar to that in those without: 31/546 (6%) vs. 23/383 (6%). Conclusions: CT scan utilization increased the appendectomy rate only in patients with a low clinical suspicion for appendicitis. Preoperative CT scans did not decrease the negative appendectomy rate.