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Necrotizing enterocolitis.

Necrotizing enterocolitis is a relatively common disorder of unknown etiology that primarily affects premature newborns. The majority of babies with necrotizing enterocolitis respond to nonsurgical management, and, despite an increase in the number of premature infants, the surgical mortality rate has improved. This review provides an overview of the current literature covering new developments in etiology, risk factors, pathogenesis, diagnosis, therapy, outcome, and preventable measures related to necrotizing enterocolitis.

Animals↗

New concepts in necrotizing enterocolitis.

Necrotizing enterocolitis is an overwhelming gastrointestinal emergency that primarily afflicts premature infants born weighing less than 1500 g. Despite years of investigation, the etiology remains unclear, and accepted prevention and treatment strategies are lacking. Studies published over the last year have provided new insight into several aspects of this complex disease. In this review, novel information is presented on (1) the epidemiology; (2) methods of early diagnosis, such as abdominal magnetic resonance imaging; (3) the importance of risk factors, including assessment of feeding strategies and role of bacterial colonization; (4) the pathophysiology, highlighting experimental and clinical trials evaluating the role of inflammatory mediators and growth factors on the disease; (5) preventive strategies, such as anaerobic bacterial supplementation; and (6) surgical interventions, including peritoneal drainage. Understanding some of these important aspects of necrotizing enterocolitis may help improve the outlook of patients with this dreaded disease. Although the incidence of neonatal necrotizing enterocolitis (NEC) and the mortality stemming from this disease have not significantly improved over the last 30 years, there is exciting new information that may significantly improve the outlook of patients with this overwhelming intestinal emergency in the near future.

Enterocolitis, Necrotizing↗

Enterocolitis caused by methicillin-resistant Staphylococcus aureus: molecular characterization of respiratory and digestive tract isolates.

We investigated the mechanism of outbreak of enterocolitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Five epidemiological markers [coagulase type, enterotoxin type, toxic shock syndrome toxin-1 (TSST-1) production, beta-lactamase production and pulsed-field gel electrophoresis (PFGE)] of 45 strains of MRSA isolated simultaneously from the respiratory tract (nasal cavity and/or pharynx and/or sputum) and stool (plus one sample of gastric juice) in 13 patients (8 males and 5 females, mean age, 77.1 years) were compared retrospectively. Forty-four of the 45 isolates of MRSA were positive for enterotoxin C and TSST-1 production, and the remaining isolate was positive for enterotoxin A and negative for TSST-1 production. All isolates were coagulase type II, and 27 showed beta-lactamase production. The patterns of coagulase type, enterotoxin type, TSST-1 and beta-lactamase production of MRSA isolated from the respiratory tract were similar to those of MRSA isolated from the intestine in 12 of 13 patients. Molecular typing by PFGE demonstrated that the pattern of respiratory tract isolates was identical to those of stool isolates in 9 (69.2%), similar in 3 (23.1 %), and different in 1 (7.7%). The data suggested that enterocolitis might be caused by the MRSA colonized in the respiratory tract and incorporated into the digestive tracts. Therefore, we propose that early eradication of MRSA in the respiratory tract is important for protection of patients against the development of enterocolitis, particularly in susceptible patients, e.g., immunocompromised or pre-operated patients with digestive diseases, especially malignant disease.

Aged↗

Prospective oral food challenge study of two soybean protein isolates in patients with possible milk or soy protein enterocolitis.

The soybean protein isolate used in powdered soybean formula is hydrolyzed more extensively than the isolate which is used in liquid soybean formula in most commercial soybean formulas. Previous in vitro studies have shown differences in human antibody response to these soybean protein isolates. Therefore, a prospective clinical study was undertaken to determine if there were differences in adverse reaction rates to these soybean protein isolates. Forty-three patients with possible milk- and/or soy-protein enterocolitis were enrolled in this study. Patients had 3 separate oral food challenges; using milk formula, soybean powder formula and soybean liquid formula. Ten (23%) patients challenged with milk had positive challenges. Fourteen (33%) patients challenged with powdered soy formula had positive challenges while thirteen (30%) challenged with liquid soy formula had positive challenges. In the 10 patients with positive milk challenges, 6 (60%) had a positive soy challenge. In the group with positive soy challenges, 5 reacted to the powdered soy challenge done first, but not the second challenge with the liquid soy formula, and 4 patients reacted to the liquid soy formula challenge done first, but not the second challenge with the powdered soy formula. These results indicate that a significant number of patients with milk protein enterocolitis have soy protein enterocolitis. In addition, an order effect can be demonstrated in the soy challenges because of the tendency to react to the first soy challenge regardless of the type of isolate. These results suggest that a local immune effect caused by the protein may be present.

Child, Preschool↗

Necrotising enterocolitis associated with invasion by Clostridium septicum complicating cyclic neutropaenia.

A fatal case of necrotising enterocolitis complicating cyclic neutropaenia in a 17-year-old boy is reported. The episode of enterocolitis was characterised by fulminant, generalised peritonitis associated with necrosis and gas formation in the wall of the ileum and caecum. Clostridium septicum was grown from premortem blood cultures and Gram positive bacilli typical of this organism were present in histological sections of the bowel wall. Necrotising enterocolitis in this and previously reported cases of cyclic neutropaenia resembles the agranulocytic form of intestinal necrosis which occasionally complicates leukaemia.

Adolescent↗

Tropical enterocolitis in children.

Besides classical necrotizing enterocolitis (in neonates), which is seen in India as elsewhere in the world, we observe sporadic cases of tropical enterocolitis, i.e. segmental jejunitis, ileitis or colitis and rarely duodenitis. This is a distinct clinico-pathological entity presenting as "acute abdomen", with pain, bilious vomiting, constipation or bloody diarrhoea. The clinical course is not as fulminating as neonatal necrotizing enterocolitis. Most cases are salvaged by conservative treatment especially after the confidence brought by laparoscopic vision of the abdomen, thus excluding perforation or gangrene of the bowel involved. Without laparoscopy, most of the cases end up in laparotomy. The pathology appears to be a kind of local hyperimmune reaction in the segment of bowel involved, ranging from punctate haemorrhages in the seromuscular layer of the bowel to a generalized red fiery look or perforation due to mucosal ulceration. Whatever the causative agent, the pathogenesis is of local vasculitis leading to ischemia and various patterns of disease.

Child, Preschool↗

Effect of oral administration of Butyrivibrio fibrisolvens MDT-1 on experimental enterocolitis in mice.

Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (10(9) CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture supernatant inhibited the growth of nine clinical isolates of Campylobacter jejuni and Campylobacter coli that could potentially cause enterocolitis. Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in colonic tissue, increased numbers of C. coli in the cecum, and decreased body weight gain. However, administration of MDT-1 to mice, prior to and during C. coli infection, reduced these effects. These results suggest that Campylobacter-induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic.

Administration, Oral↗

Absence of all components of the flagellar export and synthesis machinery differentially alters virulence of Salmonella enterica serovar Typhimurium in models of typhoid fever, survival in macrophages, tissue culture invasiveness, and calf enterocolitis.

In this study, we constructed an flhD (the master flagellar regulator gene) mutant of Salmonella enterica serovar Typhimurium and compared the virulence of the strain to that of the wild-type strain in a series of assays that included the mouse model of typhoid fever, the mouse macrophage survival assay, an intestinal epithelial cell adherence and invasion assay, and the calf model of enterocolitis. We found that the flhD mutant was more virulent than its parent in the mouse and displayed slightly faster net growth between 4 and 24 h of infection in mouse macrophages. Conversely, the flhD mutant exhibited diminished invasiveness for human and mouse intestinal epithelial cells, as well as a reduced capacity to induce fluid secretion and evoke a polymorphonuclear leukocyte response in the calf ligated-loop assay. These findings, taken with the results from virulence assessment assays done on an fljB fliC mutant of serovar Typhimurium that does not produce flagellin but does synthesize the flagellar secretory apparatus, indicate that neither the presence of flagella (as previously reported) nor the synthesis of the flagellar export machinery are necessary for pathogenicity of the organism in the mouse. Conversely, the presence of flagella is required for the full invasive potential of the bacterium in tissue culture and for the influx of polymorphonuclear leukocytes in the calf intestine, while the flagellar secretory components are also necessary for the induction of maximum fluid secretion in that enterocolitis model. A corollary to this conclusion is that, as has previously been surmised but not demonstrated in a comparative investigation of the same mutant strains, the mouse systemic infection and macrophage assays measure aspects of virulence different from those of the tissue culture invasion assay, and the latter is more predictive of findings in the calf enterocolitis model.

Animals↗

Proctoscopy in infancy with reference to its use in necrotising enterocolitis.

Experience with the fairly simple and safe technique of proctoscopy in an infant using an ordinary auroscope is reported. The use of the auroscope showed the presence of a frank colitis in 13 of 14 consecutive cases of necrotising enterocolitis. A prospective study was made during a 6-month period of 51 infants with diarrhoea referred to a gastroenterology isolation unit; proctoscopic findings that suggested colitis were found in 10. Of these, 3 appeared to have necrotising enterocolitis; 3 had salmonella or shigella dysentery; in 3 of the remaining 4 the findings were localised to the anus, with normal mucosa above. This was attributed to a mild rectal prolapse on straining. There was no correlation between the severity of the diarrhoea and the presence of colitis. Proctoscopy is safe and valuable in the early diagnosis of necrotising enterocolitis. It is also helped in assessing the progress of the disease.

Acute Disease↗

Microbiological studies of the enterocolitis of Hirschsprung's disease.

The results of a prospective study of 20 cases of newly diagnosed Hirschsprung's disease (nine of whom developed enterocolitis) and 10 normal controls showed no variations in the bacterial flora (including Clostridium difficile) in the stools of the groups studied. Viral studies showed that rotavirus was present in the stools of seven of the nine cases of enterocolitis during the episode. We suggest that Hirschsprung's enterocolitis may have a complex infective aetiology and that rotavirus plays a part.

Bacteria↗

Gastroenteritis with necrotizing enterocolitis in premature babies.

Eleven premature babies developed necrotizing enterocolitis in an epidemic of gastroenteritis and salmonella infection. This occurred in one of two premature baby wards over a period of 10 weeks. All affected babies had severe gastroenteritis and six had salmonella infection. No cases of necrotizing enterocolitis occurred in the unaffected ward during the same period. All other possible factors which might have predisposed to necrotizing enterocolitis occurred with equal frequency in both wards.There seems little doubt that infection was the significant factor in the pathogenesis.

Black or African American↗

Mild form of neonatal necrotizing enterocolitis masked by anal fissures.

In three infants with clinically mild necrotizing enterocolitis, heme-positive stools were initially attributed to anal fissures, delaying diagnosis and treatment of the enterocolitis for 4-10 days. Radiographically, pneumatosis intestinalis involved the entire colon and rectum. A causal relation may exist between necrotizing enterocolitis and anal fissure.

Enterocolitis, Pseudomembranous↗

Intussusception associated with necrotizing enterocolitis.

Two premature infants whose clinical picture initially was that of necrotizing enterocolitis eventually developed intussusception. The symptomatology of these two conditions is similar, and when they coexist, recognition of a complicating intussusception is difficult. The pathogenic relationship between necrotizing enterocolitis and intussusception remains obscure. The possibility that necrotizing enterocolitis can be a leading point in the development of intussusception is discussed.

Enterocolitis, Pseudomembranous↗

Age at onset of necrotizing enterocolitis: an epidemiologic analysis.

We studied the epidemiologic interrelationships among birth weight, gestational age, and age at onset of necrotizing enterocolitis of the newborn. As birth weight increased, the range of ages at onset and the mean age at onset both decreased. Weekly birth weight-specific attack rates for necrotizing enterocolitis declined sharply in all birth weight groups when the equivalent of 35-36 wk gestational age was reached. Our data are consistent with the hypothesis that the risk period for necrotizing enterocolitis is determined primarily by the maturity of the gastrointestinal tract of the newborn.

Age Factors↗

Inflammatory response in enterocolitis in the piebald lethal mouse model of Hirschsprung's disease.

Mucosal immune defense responses in two clinical forms of enterocolitis complicating congenital megacolon in the piebald lethal mouse model of Hirschsprung's disease were investigated. Significant histological and immunocytochemical differences were seen in the ganglionic segment of colon between piebald mice with early clinical onset of acute illness and piebald mice with late onset enterocolitis. The number of IgA-containing plasma cells infiltrating the lamina propria of the gut in the former group were significantly increased (p less than 0.001) compared to the latter group of mice and healthy controls. This study suggests that the two forms of enterocolitis complicating congenital megacolon in piebald mice have different etiologies.

Animals↗

[Campylobacter enterocolitis complaining of melena].

A 38-year-old man was admitted to our hospital complaining of 5 episodes of melena without abdominal pain or diarrhea. No abnormalities were noted through an upper gastrointestinal endoscopy, but a proctoscopy revealed a large amount of coagulated blood within the rectum immediately before his admission. A colonoscopy revealed spotty redness with dark-red coagulation in the region from the splenic flexure down to the rectum except oral colon beyond the transverse colon. A presumptive diagnosis of campylobacter enterocolitis was made by a microscopy performed on the stool specimen, then an oral administration of erythromycin was started. A colonoscopy done on the 5th hospital day proved improvement on the mucosal changes. The final diagnosis of campylobacter enterocolitis was made by the stool culture. The patient took a satisfactory course of hospitalization and was discharged on the 10th day. Bacteriological examination of stool specimen together with endoscopy has been confirmed to be useful for the diagnosis of melena cases without manifestation of infectious enterocolitis.

Adult↗

Spontaneous resolution of colonic strictures caused by necrotizing enterocolitis: therapeutic implications.

Colonic strictures are now a well recognized complication in infants surviving necrotizing enterocolitis. We describe the clinical course of seven infants with colonic strictures after necrotizing enterocolitis. Only two demonstrated the finding of fixed fibrotic stricture described in the literature, while the remaining five showed atypical radiographic and pathologic features. Two of the five showed partial or spontaneous resolution of post-necrotizing enterocolitis colonic stenoses on follow-up barium enema studies. In three of four patients with colonic resections, the histopathologic examination revealed a surprising absence of irreversible fibrosis or cicatrix formation. Current surgical practice dictates elective resection of these narrowed colonic segments. The radiologic and pathologic findings in our series of patients suggest surgical resection may be unnecessary in selected cases.

Colon↗

[First documented case of enterocolitis in Yugoslavia caused by enterohemorrhagic Escherichia coli O157].

A 'new' group of pathogenic agents, enterohemorrhagic Escherichia coli (EHEC) (particularly the strains of O157 serogroup), emerged in the last 20 years, causing an increased number of sporadic and epidemic diarrhoeal diseases with hemorrhagic enterocolitis as a most common clinical manifestation of the infection. As a consequence of the absorption and cytotoxic effect of the main virulence factor of these bacteria--verotoxin (shiga-toxin), in about 10% of the affected persons extraintestinal complications, most frequently hemolytic-uremic syndrome (HUS), occurred 7-14 days after an episode of diarrhoeal disease. The first case of hemorrhagic enterocolitis with the documented EHEC O157 infection in Yugoslavia is presented in this paper. Considering the existing expansion trend of these carriers, practitioners should be aware of them in case of the occurrence of diarrhoeal disease, (particularly hemorrhagic enterocolitis), and keep these patients under control during the reconvalescence period because of potential development of extraintestinal complications, such as HUS.

Aged↗