Poor Feeding and Emesis in a 1-day-old Male

Abstract

A 1-day-old term male infant presents with poor feeding and emesis.Complete blood count, blood culture, and cerebrospinal fluid studies are sent for evaluation of sepsis, along with studies for HSV. The patient is started on ampicillin, gentamicin, and acyclovir. An abdominal radiograph (Radiograph) demonstrates markedly dilated bowel loops, although normal-caliber small bowel loops also are seen.The evaluation for sepsis appears negative. An orogastric tube is placed for suctioning, and surgical consultation is obtained.A colon enema contrast study (Enema study) does not reveal a transition zone. A moderate amount of meconium is expelled during the study. The distended bowel loops all fill with contrast during the study, suggesting that most of the distension is occurring in the large bowel. Although distended, the loops appear to be of normal caliber.An upper gastrointestinal contrast study is conducted with small bowel follow-through. In this image, residual contrast from the enema study is seen. (Upper GI)Results of the upper gastrointestinal study are normal, with a normal duodenal jejunal junction seen.Term infant presenting at 36 hours after birth with lethargy, emesis, and abdominal distension.Although the contrast enema study did not reveal a transition zone, the dilated bowel seen in that study as well as the initial abdominal radiograph suggested a mid- or distal bowel obstruction, such as seen with Hirschsprung disease.Suction rectal biopsy was performed twice at the bedside, but the specimens were inadequate for diagnosis. Therefore, the patient underwent a near-full-thickness posterior rectal biopsy in the operating room. The specimen revealed no ganglion cells and neural hypertrophy, confirming the diagnosis of Hirschsprung disease or colonic aganglionosis.The patient underwent laparoscopic-assisted endorectal pull-through procedure at 19 days after birth. Biopsies of the rectum and the sigmoid, descending, and transverse colons were obtained, and an appendectomy was performed. Ganglion cells were identified in the appendix and transverse and descending colons, but not in the rectum and sigmoid colon. The surgeon pulled through an area proximal to the biopsy site of the descending colon near the splenic flexure as a neoanus. This site also was biopsied and demonstrated ganglion cells.Proximal obstructions generally do not present with generalized distension unless perforation has occurred. When the obstruction is distal, as in malrotation with volvulus and meconium ileus, bilious vomiting may be seen. An important historic factor is the passage of meconium, which is delayed or absent in distal obstructions, such as Hirschsprung disease or meconium plug syndromes. However, even in Hirschsprung disease, 50% of affected infants pass meconium by 24 hours of age.Physical examination findings may include masses in meconium ileus/pseudocyst. Tenderness and erythema suggest perforation or peritonitis. Surgical consultation should be obtained while the patient is made NPO and an orogastric tube is placed to suction for decompression. Patients who have sepsis or other critical illness may present with signs of abdominal distension or obstruction and should be treated for possible infection and stabilized prior to determining the cause of obstruction. Fluid resuscitation should be provided. Plain films should be obtained to rule out perforation or necrotizing enterocolitis, but they often reveal only nonspecific findings of bowel distension. The next step in radiographic evaluation often is a contrast enema. If that shows normal results, an upper gastrointestinal contrast series may be warranted. An upper gastrointestinal radiographic study may be the first evaluation if the clinical picture is highly suggestive of malrotation with volvulus.Hirschsprung disease is named after a Danish pediatrician who reported the cases of two boys who had congenital megacolon and died from severe constipation and distension in 1888. The disorder occurs in 1 in 5,000 live births and is characterized by aganglionosis in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the distal colon. Males are affected more than females. In 80% of cases, only the rectum and sigmoid colon are involved. In the remaining 20% of cases, the aganglionic component extends to the proximal colon.There is an increased risk of the disorder in siblings (2.4% to 9%) compared with the general population. Autosomal dominant, autosomal recessive, and polygenic forms have been described. It is seen in association with genetic syndromes such as Down syndrome and Waardenburg syndrome. Eight genes have been implicated in Hirschsprung disease. The receptor tyrosine kinase RET proto-oncogene is involved in 50% of nonsyndromic cases. Receptor tyrosine kinases are cell surface molecules that are involved in signal transduction for cell growth and differentiation. RET is expressed in the developing nervous system. One autosomal dominant form of Hirschsprung disease has been mapped to chromosome 10q11.1, with an associated mutation in RET. Work continues on elucidating the genetics of the disorder.In select uncomplicated cases, surgical correction can be accomplished by laparoscopically assisted primary pull-through or transanal pull-through procedures. If the patient has signs of enterocolitis, is critically ill, or has significant proximal distension, a staged reconstruction is undertaken, with initial colostomy and subsequent anastomosis, when the patient is deemed ready.The presence of a rectosigmoid transition zone on barium enema examination is highly predictive of Hirschsprung disease. However, a negative enema examination does not necessarily rule out disease. The level of the transition zone on radiographic analysis does not always predict the pathologic transition zone, particularly in long-segment disease.Anorectal manometry is another method of diagnosing Hirschsprung disease. False-positive and false-negative results are potential problems with this test. In one series of children, a definitive diagnosis was made in 95% of patients. However, this number was decreased to 81% for patients in the immediate neonatal period. Anorectal manometry may be useful in the context of predicting the absence of disease when the result is clearly negative, but for definitive diagnosis, supplemental testing often is required.Rectal suction biopsy is diagnostic and should be performed when Hirschsprung disease is suspected. However, as seen in this case, a full-thickness biopsy is necessary to confirm the diagnosis when suction biopsy specimens are inadequate. Radiographic studies and manometry are least sensitive in the immediate newborn period. Thus, if Hirschsprung disease is suspected in the first few days after birth, biopsy often is the most useful evaluation. As in this case, the diagnosis may be somewhat delayed due to the necessity of waiting for results before proceeding to the next evaluation.Acetylcholinesterase histochemistry also has been used by pathologists to diagnose Hirschsprung disease. Disease is suggested by the presence of many coarse discrete cholinergic fibers in the muscularis mucosae and in the immediately subjacent submucosa.This 19-day-old infant was diagnosed with Hirschsprung disease by biopsy and subsequently underwent resection of the aganglionic segment of the bowel. The colon resection demonstrated neural hypertrophy and lack of ganglion cells distally. Ganglion cells were identified between the muscle layers of the muscularis propria in the proximal segment of the resected colon. In Hirschsprung disease, the narrowed distal bowel segment shows an absence of ganglion cells in both the submucosal plexus and the myenteric plexus. There usually is an associated hypertrophy of the muscularis mucosa layer and neural hypertrophy in the submucosa and in the muscularis propria, as seen in this case.This slide (slide 1) of the proximal colon reveals ganglion cells (the cells with the prominent nucleoli and purplish cytoplasm).This slide (slide 2) of the proximal colon also demonstrates one ganglion cell.In this slide (slide 3) of the distal resected colon, there are no ganglion cells, and neural hypertrophy is demonstrated.This slide (slide 4) of the distal colon also lacks ganglion cells and has neural hypertrophy.Henry Lee, MD* and JoDee M. Anderson, MD***Division of Neonatology, Stanford University, Stanford, California and **Division of Neonatal-Perinatal Medicine at UT Southwestern, Dallas, Texas.