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Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids.

Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.

Animals↗

[Advances in necrotizing enterocolitis].

OBJECTIVE: To evaluate recently reported findings on necrotizing enterocolitis, Paying particular attention to pathogenesis, management and preventative strategies. DATA SOURCES: The articles covered in this report consist of randomized and quasi-randomized trials, case control studies, meta-analyses and reviews published recently. Certain other articles were also included because of their utmost importance to the subject. RESULTS: Necrotizing enterocolitis remains a major cause of morbidity and mortality in preterm infants. Those who are born with intra-uterine-growth retardation are at a several-fold increased risk. Possible pathophysiologic processes beginning in utero and continuing after birth are discussed in this review. Other factors involved in the process are related to the role of arginine and the production of intestinal nitric oxide and the action of epidermal growth factor in the regulation of cell regeneration. Perforated necrotizing enterocolitis is a complex surgical problem; definitive evidence-based guidelines for the best approach are yet to be determined. After surgery, although residual small bowel length and the presence of the ileo-cecal valve remain important predictors of duration of parenteral nutrition in infants, other factors, such as the early use of breast milk or amino acid-based formula, may also play a role in intestinal re-adaptation. Prevention strategies have centered on feeding practices and emerging experiments such as amino acid supplementation, are also discussed. CONCLUSION: Significant results in terms of mortality and morbidity will be achieved through better understanding of necrotizing enterocolitis pathogenesis and clinical and surgical management in addition to the employment of preventative strategies.

Enterocolitis, Necrotizing↗

[The role of certain Campylobacter types in the etiology of enterocolitis].

BACKGROUND: In recent decades, medical community has increasingly been calling attention to the importance of Campylobacter as an disease-causing agent in humans. Nowadays, Campylobacter jejuni (C. jejuni) is known as the most frequent bacterial cause of diarrhea worldwide. Epidemiological differences of the infections caused by Campylobacter, present in the developed and the developing countries, are attributed to the differences of the types of virulence. Due to the specificity, and the demanding features of Campylobacter, as well as poorly equipped microbiological laboratories, campylobacteriosis is insufficiently studied in our country. This investigation aimed to determine the participation of some Campylobacter species in the etiology of diarrheal diseases in our population. METHODS: The four-years continuous monitoring of Campylobacter presence was performed in the faeces of 12,605 patients with enterocolitis. The control group included 5,774 examinees of healthy children and youth. Faeces samples were cultivated on Skirrow's selective medium, and further incubated according to effective methodology for Campylobacter. Identification of strains was based on morphological, cultural and physiologic features of strains (oxidase test, catalase test, susceptibility to nalidixic acid, and hypurate hydrolysis). As a statistical method, for data processing, chi 2 test and Fisher's exact test were used. RESULTS: Campylobacter was proven in 3.86% of enterocolitis patients, and in 0.71% of healthy population. Out of 518 Campylobacter isolates, 86.48% belonged to enterocolitis outpatients, and 13.51% to inpatients. Predominant symptoms of the disease were diarrhea (81.83%), increased temperature (34.71%), vomiting (19.77%), and stomach pain (15.17%). The diseased were predominantly infants in the first year of life. Out of 300 Campylobacter isolates, 75% were identified as Campylobacter jejuni, 23% as Campylobacter coli (C. coli), and 2% as Campylobacter lari (C. lari). CONCLUSION: Species of Campylobacter genus participate in the etiology of enterocolitis at 3.86%. According to numerous parameters the infection in our population coincides with the infection in the population of European countries. Frequent findings of C. coli in our region are in discrepancy with the results of numerous studies conducted in the developed countries.

Campylobacter Infections↗

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats.

BACKGROUND: Administration of methotrexate (MTX) to rats fed an elemental diet results in a high mortality from severe enterocolitis. Previous studies have shown that pectin is an important precursor of substrates for intestinal structure and function and may facilitate intestinal recovery after enterocolitis. The aim of this study is to evaluate the effect of pectin on MTX-induced enterocolitis in rats. METHODS: Rats received intragastric infusion of either 1% pectin-supplemented or pectin-free elemental diet from the beginning of the study via a gastrostomy. On the 4th day animals received either MTX, 20 mg/kg intraperitoneally, or saline injection and were killed on the 7th day for sampling. RESULTS: Pectin supplementation significantly decreased body weight loss, organ water content, and intestinal myeloperoxidase levels and increased mucosal protein, DNA, and RNA content in enterocolitis rats. The intestinal permeability was increased by administration of MTX, and pectin supplementation significantly reversed the increased permeability in the distal small bowel and colon. Pectin supplementation also lowered the magnitude of bacterial translocation, decreased plasma endotoxin levels, and restored bowel microecology. CONCLUSIONS: Pectin significantly decreased MTX-induced intestinal injury and improved bowel integrity.

Animals↗

Prestenotic enteritis and enterocolitis in children: Description of a syndrome and review of five cases.

A clinical syndrome of prestenotic enteritis and enterocolitis consisting of abdominal distention and pain, intermittent diarrhea and constipation, failure to thrive, fever and in some patients, extreme prostration and death is described. The pathogenesis of this enteritis and enterocolitis apparently is related to partial mechanical obstruction of the bowel with proximal dilatation, stagnation, and capillary stasis. Acute relief from the enteritis and enterocolitis may be obtained by stomal dilatation and colonic irrigation; however, all patients in our series required surgical intervention. because mortality in this disease is significant and the results with early surgical intervention are favorable, surgical intervention is encouraged at the first sign of prestenotic enteritis or enterocolitis in children. Surgical correction of the distal stenosis produced a growth spurt in the two successfully treated patients without other growth-limiting disease.

Abnormalities, Multiple↗

Pediatric Salmonella enterocolitis in a teaching hospital in Taitung: A four-year analysis.

In order to understand the childhood Salmonella enterocolitis in Taitung, we retrospectively collected the patients with the diagnosis of acute enterocolitis who were admitted to the pediatric wards of Taitung branch of Mackay Memorial Hospital from January 1, 1995 to December 31, 1998. Salmonella enterocolitis accounted for 16.8% of the total cases of acute enterocolitis. The mean age of the patients was 14.6 +/- 14.1 months old. Seventy-nine patients were male and 78 patients were female. Eighty-two patients lived in the urban area and 75 patients lived in the suburbs. The mean duration from onset of illness to admission was 2.6 +/- 1.9 days. The mean duration of hospitalization was 6.6 +/- 4.8 days. The peak incidence was in August and September. The most common clinical manifestations were fever (74.5%) and blood stool (46.5%). In 157 patients, Salmonella serogroup B was isolated from stool in 115 patients. The rate of bacteremia was 4.5%. Serogroup D accounted for 28.6% of the bacteremia. Two patients developed meningitis and one patient had osteomyelitis. Of 88 patients examined for rotavirus, 12 had positive results. There was neither bowel perforation nor mortality recorded in our study.

Bacteremia↗

Cocaine: a risk factor for necrotizing enterocolitis.

Necrotizing enterocolitis occurs most often in the small preterm infant, usually with birthweight less than 1.5 kg. Necrotizing enterocolitis has also been described in more mature infants, however, often the result of reduced gastrointestinal blood flow. We describe four relatively large infants from our nursery with varying severity of necrotizing enterocolitis. None had any of the known risk factors; all had a history of maternal cocaine use. Two were initially cared for in the term nursery. All four presented with abdominal distention, bloody stools, vomiting, or residuals. One infant presented with fulminant deterioration and subsequently died; the other three infants were treated medically and survived. It is suggested that a high index of suspicion be maintained for the possibility of necrotizing enterocolitis and feeding intolerance in term and near-term infants exposed in utero to cocaine.

Cocaine↗

Gastrointestinal adenovirus: an important cause of morbidity in patients with necrotizing enterocolitis and gastrointestinal surgery.

Adenoviruses have recently been recognized as etiologic agents of enteric disease in hospitalized infants and young children. Patients who have undergone surgical procedures related to the complications of neonatal necrotizing enterocolitis constitute a population of infants who are often hospitalized for extended periods of time. We studied the incidence of enteric adenovirus infections in infants with necrotizing enterocolitis who had undergone intestinal surgery resulting in colostomies or ileostomies. These studies revealed that 31.7% of the hospital admissions in such patients were complicated by symptomatic infection with enteric adenoviruses. The rate of adenovirus infection in this population was significantly higher than the rate of such infections encountered in infants undergoing ostomy procedures for other conditions and in age-matched hospitalized infants without prior gastrointestinal surgery. The infections with enteric adenovirus were generally accompanied by an increase in intestinal output which was temporally associated with the excretion of adenovirus in the intestinal fluid. In addition infections with enteric adenoviruses in the infants with necrotizing enterocolitis and ostomies were associated with a marked increase in length of hospitalization as compared to uninfected infants with similar underlying gastrointestinal pathology. Epidemiologic analysis revealed that many of the cases of enteric adenovirus infection in the study population occurred during seasons in which enteric adenovirus infections were prevalent in the hospital population. These studies demonstrate that enteric adenovirus infections are major causes of morbidity in hospitalized patients who have of morbidity in hospitalized patients who have undergone ileostomy or colostomy procedures for necrotizing enterocolitis and that the prevention of enteric adenovirus infections might result in a significant improvement in the hospital care of infants with these conditions.

Adenoviridae Infections↗

[Human colostrum in the prevention of diarrhea and necrotizing enterocolitis].

The effect of human colostrum in the prevention of diarrhea and necrotizing enterocolitis, as well as the advantages of its use in gastroenteritis, was studied in 71 premature newborns. The frequency of diarrhea and enterocolitis in 16 healthy newborns who were given human colostrum (group II), was less than in the 22 healthy newborns who received only cows milk (group I), but without statistical significance. In 25 infants with diarrhea who were given human colostrum, the frequency of enterocolitis and sepsis (group IV) was less than in the 8 infants with diarrhea who didn't receive human colostrum (group III). At the end we suggest that human colostrum should be given in high risk infants in order to decrease the frequency of diarrhea and enterocolitis and we also make some recommendation as to how to obtain and store human colostrum.

Biological Products↗

Intussusception associated with Salmonella typhimurium enterocolitis.

Intussusception in the adult is unusual, and its etiology is mostly neoplastic. In most cases of intussusception, a polypoid tumor located in the terminal ileum invaginates within the cecum. We described an unusual case of adult intussusception associated with Salmonella typhimurium enterocolitis. Preoperative diagnosis of intussusception in the ileocecal region was made by ultrasonography, and the ileocecal region containing the mass in the cecum, causing the intussusception, was resected. Histological features of the mass included an edematous focal wall thickening. Later, the diagnosis of S. typhimurium enterocolitis was made by the preoperative stool cultures. This case demonstrated intussusception as a complication of S. typhimurium enterocolitis. It is worth noting that S. typhimurium enterocolitis is in fact a potential cause of intussusception.

Cecal Diseases↗

Activation of the kallikrein-kinin system in arthritis and enterocolitis in genetically susceptible rats: modulation by a selective plasma kallikrein inhibitor.

We have developed models of acute and chronic inflammatory arthritis and enterocolitis using peptidoglycan-polysaccharide injected intraperitoneally or subserosally (intramurally) into the distal ileum and cecum. Acute inflammation occurs in both Buffalo and Lewis rats, characterized by inflammation of the injected areas of the intestine. However, only the genetically susceptible Lewis rat develops chronic synovitis and joint erosion or adhesions and granulomatous enterocolitis. In the Lewis rat but not the Buffalo rat, these changes are accompanied by a decrease in plasma prekallikrein and high-molecular-weight kininogen, reflecting activation of the kallikrein-kinin system. Pretreatment with a specific plasma kallikrein inhibitor modulates the acute and chronic arthritis. The same inhibitor partially abrogates the acute changes characteristic of enterocolitis, and preliminary data suggest similar results in the chronic model. The results of these studies indicate that the kallikrein-kinin system plays an important role in arthritis and enterocolitis induced by bacterial products and that kallikrein inhibitors are potential therapeutic agents for inflammatory arthritis and inflammatory bowel disease.

Acute-Phase Proteins↗

Neutropenic enterocolitis in adult leukemias.

Neutropenic enterocolitis is a frequent autopsy finding in adult patients with acute leukemias. The predisposing factors other than neutropenia are not clear. There are also contradictions about treatment. Therefore, this entity still presents a diagnostic and therapeutic dilemma for clinicians. This retrospective study was performed to determine the incidence of neutropenic enterocolitis in adult leukemic patients, to examine the possible risk factors, clinical characteristics and treatment outcome. The pathogenesis is also discussed considering clinical and laboratory findings of the patients. The incidence of neutropenic enterocolitis was 6.5% for acute myeloid leukemia and 4.6% for acute lymphoblastic leukemia. The mean absolute neutrophil count at diagnosis was 48/mm3 (median: 0/mm3). The median duration of severe neutropenia (absolute neutrophil count < or = 500/mm3) on follow-up before the diagnosis was 32 days. Thirteen out of 20 patients had received antineoplastic drugs within the last 12 days, but 2 had not. Fourteen patients had signs of peritoneal irritation and 3 of them underwent surgery. The others received supportive measures, i.e. bowel rest, intravenous fluids, combinations of wide spectrum antibiotics, transfusions, hemodynamic supports and nasogastric decompression, if necessary. All 3 patients who underwent surgery survived, whereas only 1 of the 11 who received other treatments did. Six patients without signs of peritonitis were treated with antibiotics and the mentioned supportive measures. Four survived, but the others died due to sepsis. In conclusion, considering some recent reports that stated good outcome with conservative measures in the presence or absence of peritonitis, there is still debate regarding the optimal choice of treatment. The importance of early diagnosis cannot be overemphasized. Signs of peritoneal irritation indicate a life threatening condition. Surgery can be performed successfully in such patients. Long duration of neutropenia may be an important risk for neutropenic enterocolitis.

Acute Disease↗

Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature.

BACKGROUND: This case series with an accompanying review of the literature describes neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors. METHODS: Neutropenic enterocolitis is documented in two patients undergoing autologous stem cell transplantation. A review of MEDLINE from 1970 to the present was performed to delineate the prior related disease settings in which this condition has been described. The nature of the clinical syndrome and controversies regarding management are discussed. RESULTS: The authors report two patients who each received autologous stem cell transplantation for the treatment of a solid tumor. Both patients presented with progressive abdominal pain, signs of peritoneal irritation on examination, and pneumatosis intestinalis. In the first case, the syndrome developed rapidly over several hours, requiring emergent surgical intervention during the period of postchemotherapy nadir. In the second case, the patient developed a slowly progressive clinical picture that was managed successfully with medical therapy alone. A review of the literature suggests that neutropenic enterocolitis arises due to drug-induced bowel wall mucosal injury followed by superinfection with colonic and opportunistic organisms. Surgical intervention potentially is beneficial in patients who develop an acute syndrome that is unresponsive to antibiotic and supportive therapy. Those patients who can be stabilized with medical management often will recover once reengraftment occurs. CONCLUSIONS: Neutropenic enterocolitis is described in two patients undergoing autologous stem cell transplantation for solid tumors. The management of this life-threatening complication is controversial and governed by the nature of the clinical presentation.

Antineoplastic Combined Chemotherapy Protocols↗

Neutropenic enterocolitis in adults with acute leukemia.

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.

Acute Disease↗

Pseudomembranous and neutropenic enterocolitis in pediatric oncology patients.

Neutropenic enterocolitis in oncological patients represents a wide spectrum of clinicopathological pictures each with its own entity. Early diagnosis of enterocolitis can lead to improved supportive care and therefore better outcome. We present two cases--patient A, a child with pseudomembranous colitis caused by Clostridium difficile, and patient B, a child with neutropenic enterocolitis, where no organism was found. By allowing an insight into the pathology, immunology and culture results, we demonstrated that early diagnosis leads to improved management and therefore improved outcome.

Adolescent↗

Neutropenic enterocolitis: a rare presenting complication of acute leukemia.

Neutropenic enterocolitis is a necrotizing inflammatory process with intramural infection that occurs predominantly in neutropenic patients. This syndrome is most frequently observed after chemotherapy for hematologic and solid tissue malignancies, but it can also be observed in a number of other clinical settings as well. Neutropenic enterocolitis can be a rare presenting complication of acute leukemia. We report a case of acute lymphoblastic leukemia that presented with abdominal pain due to neutropenic enterocolitis. The diagnostic and treatment challenges associated with this manner of presentation are discussed.

Adult↗

Neutropenic enterocolitis. Clinical diagnosis and treatment.

Review of the consultation records of the Gastrointestinal Surgical Oncology service at Roswell Park Memorial Institute from 1982 to 1987 revealed 22 patients with a clinical diagnosis of neutropenic enterocolitis. Ninety-one percent of the patients had hematologic malignancies, and 95% were receiving cytotoxic chemotherapy. Sixteen patients were treated nonsurgically; 11 died. Of those 11 cases, autopsies were performed in 9. At autopsy, the clinical diagnosis was confirmed in four cases; four cases were found to have normal intestinal tracts, and one case had a small bowel volvulus. In none of the four cases for which autopsy proved neutropenic enterocolitis was transmural bowel necrosis or perforation found. Laparotomy was performed in six patients; three survived. The clinical diagnosis was verified in four of the six patients. Neutropenic enterocolitis must be considered a diagnosis of exclusion. Care of these patients should be individualized. Nonoperative management with bowel rest, decompression, nutritional support, and broad spectrum antibiotics is recommended initially. Operative intervention is recommended for those with perforation or those whose condition deteriorates clinically during close, frequent observation.

Adolescent↗

Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low-birth-weight infants.

BACKGROUND: Very premature infants fed by gavage are unable to regulate their own enteral intake. Therefore the rate at which feedings are advanced must be determined by caregivers. While advancing feedings too rapidly may increase the risk of necrotizing enterocolitis, advancing feedings too slowly might result in undernutrition or prolonged hospital stay. OBJECTIVES: For low-birth-weight premature infants receiving parenteral fluids, to assess the effect of different rates of advancement of enteral feedings beginning at the same age on measures of feeding tolerance and neonatal outcome. SEARCH STRATEGY: Search strategies included a Medline search and a search of the Oxford Database of Perinatal Trials; additional references were sought in review articles, relevant chapters of textbooks, a previous systematic review, recent American Pediatric Society - Society for Pediatric Research abstracts, personal files, and personal communication. SELECTION CRITERIA: Only randomized or quasi-randomized trials were considered. Trials were included if premature low-birth-weight infants were studied and if the strategies being compared were different rates of advancement of feedings (accomplished by either differences in volume or concentration) with the onset of feedings at the same postnatal age in each group. DATA COLLECTION AND ANALYSIS: The two reviewers reached consensus for inclusion of trials. Data regarding clinical outcomes were extracted and evaluated by the two reviewers independently of each other. Authors were contacted as needed and feasible to clarify or provide missing data. The specific data that were needed were requested in writing. MAIN RESULTS: Among infants randomized to more rapid rates of advancement of feedings, there was an overall reduction in days to full enteral feeding and days to regain birth weight. There was no effect on necrotizing enterocolitis (relative risk = 0.90, 95% confidence interval = 0. 46-1.77). REVIEWER'S CONCLUSIONS: There are suggested advantages of more rapid rates of advancing feedings in premature low-birth-weight infants (shorter time to regain birth weight and shorter time to achieve full feedings). It is unclear whether this strategy should be adopted as routine practice because of limited information regarding safety (broad confidence intervals for the incidence of necrotizing enterocolitis) and the effect on length of hospital stay (broad confidence intervals). Because different birth weight ranges and different rates of advancement were used in each of these studies, the ideal rate of advancement remains unclear, particularly for extremely-low-birth-weight infants.

Enteral Nutrition↗