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Signs and Symptoms
1. Bilious vomiting is always abnormal.
2. Abdominal distention (scaphoid abdomen possible).
3. Delayed, scanty or no passage of meconium.
4. Polyhydramnios in mother.
5. Down's syndrome
6. Family history
a. Hirschsprung's disease
b. Diabetic mother
c. Jejunal atresia
Work-up (Logical approach)
1. While the infant is being studied, it must be kept in mind that the problem may be "non-surgical".
a. Sepsis of the newborn with associated ileus is the most important cause of non-surgical bilious vomiting and abdominal distention.
b. Intracranial lesions
ii. Subdural hemorrhage
c. Renal disease associated with uremia.
i. Renal agenesis
ii. Polycystic disease
iii. Other urinary tract anomalies which may be associated with severe hydronephrosis.
2. Plain roentgenograms of the abdomen.
a. Diagnostic in complete high intestinal obstruction- no gas in distal small bowel.
i. Double bubble in duodenal obstruction.
ii. Few gas filled loops beyond duodenum indicates jejunal atresia.
b. Many gas filled loops (requires 24 hours) indicates some form of low intestinal obstruction.
i. Ileal atresia
ii. Meconium ileus (an unfortunate misnomer)- obstruction of the distal small intestine by thick undigested meconium.
iii. Meconium plug syndrome - obstruction of colon by a plug of meconium.
iv. Small left colon syndrome.
v. Hirschsprung's disease - congenital aganglionosis of colon starting with the rectum.
vi. Colonic atresia.
c. May be nonspecific in instances of malrotation of the intestines. This diagnosis must always be considered in neonates with unexplained bilious vomiting.
d. Calcifications - at some time during fetal life meconium was (is) present in the abdomen.
3. Contrast enema will differentiate the various types of low
a. Microcolon - complete obstruction of the small bowel.
b. Meconium plug syndrome - colon dilated proximal to an intraluminal mass.
c. Hirschsprung's disease - although it may appear to be diagnostic, not reliable in the newborn.
d. Small left colon syndrome - colon dilated to the splenic flexure, then becomes narrow.
4. Upper G.I. series - the procedure of choice in diagnosing malrotation of the intestines. In the past a contrast enema was thought to be the diagnostic test of choice in instances of malrotation but the cecum and ascending colon can be in normal position in an infant or child with malrotation of the intestines.
5. Rectal biopsy - a pathologist competent in reading the slides
is essential and should not be taken for granted.
a. Suction biopsy of the rectal mucosa and submucosa- best screening procedure to rule out Hirschsprung's disease (ganglion cells are present in the submucosa), and is diagnostic in experienced hands.
b. Full thickness biopsy of the rectal wall may be necessary if the suction biopsy is non-diagnostic or if the pathologist is unwilling or unable to make the diagnosis of aganglionosis on a suction biopsy specimen. This procedure is difficult in the small infant and has been replaced by the suction biopsy in most centers.
c. All newborns who have delayed passage of meconium associated with a suspicious contrast enema should have a suction biopsy of the rectal mucosa and submucosa. With this technique, Hirschsprung's disease will be diagnosed early before it is complicated with enterocolitis. If delayed passage of meconium is "cured" by rectal stimulation(suppository, thermometer, or finger), it must be kept in mind that the diagnosis of Hirschsprung's disease is still a possibility. Whether or not a suction biopsy of the rectum is done before the infant goes home depends on the clinical setting but the safe course of action is to do the rectal biopsy before discharge. Parents may not call before the infant gets into trouble with enterocolitis.
d. Suction biopsy of the rectum is probably indicated in all cases of so called meconium plug syndrome or small left colon syndrome. If the suction biopsy is not done, the infant must be observed for recurrent gastrointestinal symptoms. A breast-fed infant who has Hirschsprung's disease can "get by" for a prolonged period of time.
6. Concluding comments:
The newborn suspected of having intestinal obstruction should be studied in a logical step by step manner. It is important that it be definitely established that the infant has a surgical problem before surgery is performed. This is usually not difficult in instances of complete high small bowel obstruction or when plain films of the abdomen show calcification and/or a distal small bowel obstruction with the contrast enema showing a microcolon or a definite malrotation of the colon (cecum in upper mid-abdomen or left upper quadrant).
When plain films are suggestive of a high small bowel obstruction but there is gas in the distal small bowel, an upper GI series rather than a contrast enema should be performed. It is critically important that the diagnosis of malrotation of the intestines be always considered and ruled out in a neonate with bilious vomiting. Prompt recognition and treatment of malrotation of the intestines which is often associated with a midgut volvulus avoids the dire consequences of the problems associated with a massive small bowel resection.
Mistakes are frequently made when the contrast enema is interpreted as normal, meconium plug syndrome, small left colon syndrome or Hirschsprung's disease. In all of these clinical situations, a suction biopsy of the rectum is an excellent screening procedure. If ganglion cells are present, Hirschsprung's disease is ruled out and the infant probably has a non-surgical diagnosis. If ganglion cells are absent, the next step depends on the clinical picture and setting. If the pathologist is experienced and confident of the interpretation, the diagnosis of Hirschsprung's disease can be made with confidence. If there is any doubt about the absence of ganglion cells in the suction biopsy, a full thickness biopsy of the rectum (a difficult technical procedure requiring a general anesthetic) can be done to settle the issue. If Hirschsprung's disease is believed to be the problem, it must be diagnosed histologically before the infant is operated upon because at the time of surgery the site of obstruction may not be apparent and the abdomen may be closed because no obvious site of obstruction is found.
Hypothyroidism in the first two to three months of life can mimic Hirschsprung's disease in all aspects except for a normal rectal biopsy.
Another important point to remember is that duodenal atresia is a different disease from jejunal or ileal atresia in terms of their cause. Jejunal and ileal atresia occur as a result of a vascular accident in the small bowel mesentery during fetal life. Consequently, there is a relatively low incidence of other congenital anomalies except for cystic fibrosis.
Duodenal atresia is a different disease in that there is a very high incidence of associated anomalies-- (Down's syndrome, imperforate anus, renal anomalies, congenital heart disease, etc.).
Malrotation of the intestines and Hirschsprung’s disease must be ruled out before a newborn with unexplained bilious vomiting and/or abdominal distention is sent home. It can be unsafe to rely on parents to observe their infant for problems resulting from the above conditions. If diagnosed late, malrotation of the intestines or Hirschsprung’s disease can become life threatening or result in life long problems.
Esophageal atresia (EA) with distal tracheo-esophageal fistula
is the most common congenital
anomaly of the esophagus, followed by EA without TEF also known as pure esophageal atresia and
pure TEF. Incidence is one in every 2500 live births. The trachea and esophagus initially begin as a ventral diverticulum of the foregut during the third intrauterine week of life. A proliferation of endodermal cells appears on the lateral aspect of this growing diverticulum. These cell masses will divide the foregut into trachea and esophageal tubes. Whether interruption of this normal event leads to tracheo-esophageal anomalies, or during tracheal growth atresia of the esophagus results because of fistulous fixation of the esophagus to the trachea remians to be proven. Polyhydramnios is most commonly seen in pure EA. EA causes excessive salivation, choking, coughing, regurgitation with first feed and inability to pass a feeding tube into the stomach. Contrast studies are rarely needed and of potential disaster (aspiration). Correct dehydration, acid-base disturbances, respiratory distress and decompress proximal esophageal pouch (Reploge tube). Evaluate for associated conditions such as VACTERL association. Correct dehydration, acid-base disturbances, respiratory distress and decompress proximal esophageal pouch (Reploge tube). Evaluate for associated conditions such as VACTERL association (3 or more):
-Vertebral anomalies i.e. hemivertebrae, spina bifida
-Anal malformations i.e. imperforate anus
-Cardiac malformations i.e. VSD, ASD, Tetralogy Fallot
-Tracheo-Esophageal fistula (must be one of the associated conditions)
-Renal deformities i.e. absent kidney, hypospadia, etc.
Early surgical repair (transpleural or extrapleural) is undertaken for those babies with adequate arterial blood gases, adequate weight (>1200 gm) and no significant associated anomalies. Delayed repair (gastrostomy first) for all other patients. Repair consists of muscle-sparing thoracotomy, closure of TEF and primary anastomosis. Esophagogram is done 7-10 days after repair. Most important predictors of outcome: birth weight, severity of pulmonary dysfuntion, and presence of major congenital cardiac disease. Complications after surgery: anastomotic leak, stricture, gastroesophageal reflux, tracheomalacia and recurrent TEF. Increase survival is associated with improvements in perioperative care, meticulous surgical technique and aggressive treatment of associated anomalies.
Congenital isolated tracheo-esophageal fistula (TEF) occurs as 4-6% of the disorders of the esophagus bringing problems during early diagnosis and management. More than H-type is N-type, due to the obliquity of the fistula from trachea (carina or main bronchi) to esophageal side (see the figure) anatomically at the level of the neck root (C7-T1). Pressure changes between both structure can cause entrance of air into the esophagus, or esophageal content into the trachea. Thus, the clinical manifestation that we must be aware for early diagnosis are: cyanosis, coughing and choking with feedings, recurrent chest infections, persistent gastrointestinal distension with air, and hypersalivation. Diagnosis is confirmed with a well-done esophagogram, or video-esophagogram (high success rates, establish level of the TEF). Barium in the trachea could be caused by aspiration during the procedure. Upon radiologic doubt bronchoscopy should be the next diagnostic step. Any delay in surgery is generally due to delay in diagnosis rather than delay in presentation. Management consists of surgical closure of the TEF through a right cervical approach. Hint: a small guide-wire threaded through the fistula during bronchoscopy may be of some help. Working in the tracheo-esophageal groove can cause injury to the recurrent laryngeal nerve with vocal cord paralysis. Recurrence after closure is rare.aggressive treatment of associated anomalies.
The three most common anastomotic complications are in order of frequency: stricture, leakage and recurrent TEF. Recurrent TEF after surgical repair for esophageal atresia occurs in approximately 3-15% of cases. Tension on the anastomoses followed by leakage may lead to local inflammation with breakage of both suture lines enhancing the chance of recurrent TEF. Once established, the fistula allows saliva and food into the trachea, hence clinical suspicion of this diagnosis arises with recurrent respiratory symptoms associated with feedings after repair of esophageal atresia. Diagnosis is confirmed with cineradiography of the esophagus or bronchoscopy. A second thoracotomy is very hazardous, but has proved to be the most effective method to close the recurrent TEF. Either a pleural or pericardial flap will effectively isolate the suture line. Pericardial flap is easier to mobilize, provides sufficient tissue to use and serves as template for ingrowth of new mucosa should leakage occur. Other alternatives are endoscopic diathermy obliteration, laser coagulation, or fibrin glue deposition.
B. Gastro-Duodenal Anomalies
B.1 Gastric Anomalies
Congenital gastric outlet obstruction is extremely rare. It occurs either in the pyloric or antral region. Antral membranes (web or diaphragm) are thin, soft and pliable, composed of mucosa/submucosa, and located eccentric 1-3 cm proximal to pyloro-duodenal junction. They probably represent the developmental product of excess local endodermal proliferation and redundancy. The diagnosis should rely on history, contrast roentgenology studies and endoscopic findings. Symptoms are those of recurrent non-bilious vomiting and vary according to the diameter of aperture of the membrane. There is a slight male predominance with fair distribution between age groups in children. Associated conditions: pyloric stenosis, peptic ulcer and cardiac. History of polyhydramnios in the mother. Demonstration of a radioluscent line perpendicular to the long axis of the antrum is diagnostic of a web. Endoscopy corroborates the diagnosis. Management can be either surgical or non-surgical. Surgical Tx is successful in symptomatic pt. and consist of pyloroplasty with incision or excision of the membrane. Other alternative is endoscopic balloon dilatation or transection of the web. Non-obtructive webs found incidentally can be managed medically with small curd formula and antispasmodics. The presence of an abnormally dilated gastric bubble in prenatal sonography should alert the physician toward the diagnosis of congenital antro-pyloric obstruction.
B.2 Pyloric Stenosis
Is an abnormality of the pyloric musculature (hypertrophy) causing gastric outlet obstruction in early infancy. The incidence is 3 per 1000 live births. The etiology is unknown, but pylorospasm to formula protein cause a work hypertrophy of the muscle. Diagnostic characteristics are: non-bilious projectile vomiting classically 3-6 weeks of age, palpable pyloric muscle "olive", contrast studies are not necessary when the pyloric muscle is palpated, enlarged width and length in ultrasonography. The treatment consist in correction of hypochloremic alkalosis and state of dehydration and performing a Fredet-Ramstedt modified pyloromyotomy. Post-operative management consist of: 50% will have one to several episodes of vomiting, usually can feed and go home in 24-36 hours, initial feeds start 8-12 hours after surgery.
B.3 Duodenal Malformations
Can be intrinsic (Atresia, Stenosis, Webs) or extrinsic (Annular
pancreas, Ladd's bands). Occur distal or proximal to the ampulla of
Most commonly distal to ampulla and therefore bilious vomiting is
(Note: Bilious vomiting is surgical until proven otherwise in a baby).
"Windsock" webs have clinical importance because of their tendency to be confused with distal duodenal obstruction and because of the frequent occurrence of an anomalous biliary duct entering along their medial margin. Embryology: The first major event in the differentiation of the duodenum, hepatobiliary tree, and pancreas occurs at about the third week in gestation, when the biliary and pancreatic buds form at the junction of the foregut and the midgut. The duodenum at this time is a solid cord of epithelium, which undergoes vacuolization followed by recanalization and restitution of the intestinal lumen over 3-4 weeks of normal development. Failure of recanalization of the second part of the duodenum results in congenital obstruction of the lumen, often in conjunction with developmental malformation of the pancreatic anlagen and the terminal part of the biliary tree. In support of this concept is the high incidence of annular pancreas observed, believed to represent a persistence of the ventral pancreatic anlage in association with intrinsic duodenal obstruction.
Congenital partial obstruction of the duodenum can be either intrinsic (membrane, web or pure) or
extrinsic (Ladd's bands, annular pancreas). A significant group (25-33%) is born with Down's syndrome.
This does not entail a higher risk of early mortality unless associated with cardiac malformations. Other
associated conditions are malrotation (midgut volvulus is rare due to absent bowel distension and
peristalsis), biliary tract anomalies and Meckel's diverticulum. The diagnosis is suggested in utero by
the double-bubble image on ultrasound. Vomiting is the most frequent presenting symptom. UGIS is
diagnostic, showing a dilated stomach and first duodenal portion with scanty passage of contrast
material distally. Management varies accordingly to the type of stenosis: Ladd's bands are lysed. Pure
stenosis is opened longitudinally and closed transversely (Heineke-Mickulicz). Membranous stenosis is
resected. Successful endoscopic membranectomy of duodenal stenosis has been reported.
Duodeno-duodenostomy is the procedure of choice for annular pancreas. Diaphragms can rarely be
double. Anastomotic malfunction requiring prolonged intravenous nutrition and hospitalization has
prompted development of a diamond shape larger stoma. Tapering or plication of the dilated duodenum
is another effective method of improving disturbed transit. Other complications after surgery are
megaduodenum with blind loop syndrome, biliary reflux, cholestatic jaundice, delayed transit and bowel
obstruction. Early mortality is associated to prematurity and associated malformations. Long-term
follow-up is warranted to identify late problems.
The diagnostic characteristics are: bilious vomiting, history of polyhydramnios in mother, KUB with classic "Double-bubble" appearance, a microcolon in barium enema study or malrotation.
Treatment consist in: (1) duodeno-duodenostomy bypass for atresias, annular pancreas, and some stenosis. (2) duodenoplasty for webs, and stenosis, and (3) lysis of ladd's bands and Ladd's procedure for malrotation. Associated anomalies are: Down's syndrome (20-30%), VACTERL syndrome, CNS anomalies and cardiac anomalies.
C. Malrotation and Volvulus
The rotation and normal fixation of the intestinal tract takes
within the first three months of fetal life. In the earliest stages
the intestinal tract is recognizable as a continuous tube, the stomach,
small intestine, and colon constitute a single tube with its blood
arising posteriorly. The midgut portion of this tube, from the second
of the duodenum to the mid-transverse colon, lengthens and migrates out
into an extension of the abdomen, which lies at the base of the
cord. Here this loop of bowel undergoes a 270-degree counterclockwise
at its neck. In the center of the twisted loop lie the blood vessels
will become the superior mesenteric artery and vein. After rotation,
small intestine quite rapidly withdraws into the abdominal cavity, with
the duodenum and the proximal jejunum going first. During this process
the duodenojejunal junction goes beneath and to the left of the base of
the superior mesenteric vessels. This leaves the upper intestine,
the stomach and the duodenum, encircling the superior mesenteric
like a horseshoe with its opening on the left side of the embryo. The
intestine then follows into the abdomen, and withdrawal of the right
of the colon takes place so that it lies to the left. At the next step,
the cecum and the right colon begin to travel across the top of the
mesenteric vessels and then down to the right lower quadrant. The colon
now lies draped across the top of the superior mesenteric vessels,
like a horseshoe, with its opening placed inferiorly. The
loop is said to attach to the posterior abdominal wall soon after its
whereas the mesenteric attachments of the entire colon and of the
small bowel gradually adhere after they arrive in their normal
In malrotation the right colon can create peritoneal attachments that
and obstruct the third portion of the duodenum (Ladd's bands).
The diagnostic hallmarks are: bilious vomiting (the deadly vomit), abdominal distension and metabolic acidosis. A UGIS is more reliable than barium enema, most patients present in first month of life (neonatal), but may present at any time.
The treatment is immediate operation; volvulus often means strangulation. Needs fluid and electrolyte replacement. Ladd's procedure consist of: reduce volvulus with a counterclockwise rotation, place small bowel in right abdomen, lysed ladd's bands, place large bowel in left abdomen, do an appendectomy. In cases of questionable non-viable bowel a second look procedure is required.
Meconium ileus is a neonatal intraluminal intestinal obstruction caused by inspissated meconium blocking the distal ileum. Occurs in 10-15% of all patients with cystic fibrosis, and 85-95% of patients with meconium ileus have cystic fibrosis. The meconium has a reduced water, abnormal high protein and mucoproteint content, the result of decreased pancreatic enzyme activity and prolonged small bowel intestinal transit time. Meconium Ileus is classified into two types: (1) Simple meconium ileus: The distal small bowel (10-30 cm of distal ileum) is relatively small, measuring less than 2 cm in diameter and contains concretions of gray, inspissated meconium with the consistency of thick glue or putty. It is often beaklike in appearance, conforming to the shape of the contained pellets. Proximally, the mid-ileum is large, measuring up to 7 cm in diameter. It is greatly distended by a mass of extremely thick, tenacious, dark green or tarry meconium. The unused small colon (microcolon) contains a small amount of inspissated mucus or grayish meconium. (2) Complicated meconium ileus: usually occurs during the prenatal period associated to volvulus, atresias, gangrene, perforation or peritonitis. A cystic mass or atresia of the bowel may occur. The degree of obstruction varies, may be cured in mild cases by rectal irrigations. Failure to pass meconium, abdominal distension and vomiting are seen in more severe cases. The diagnosis is suspected with findings of: multiple loops of dilated small bowel and coarse granular "soap-bubble" appearance on plain abdominal films. Some cases may show calcifications in the peritoneum (Meconium peritonitis). The Sweat Test is diagnostic of cystic fibrosis (value over 60 meq/L of sweat sodium or chloride are diagnostic). This test is not useful in infant during first weeks of life. Therapy is either: (1) Nonoperative- should be tried first. It consist of a careful gastrograffin enema after the baby is well-hydrated. Gastrograffin is a hyperosmolar aqueous solution of meglumine diatrizoate containing 0.1% polysorbate-80 (tween-80, a wetting agent) and 37% iodine. Its success is due to the high osmolarity (1700 mosm/liter) which draws fluid into the bowel and softens and loosens the meconium. (2) Surgical therapy that has included: ileostomy with irrigation, resection with anastomosis, and resection with ileostomy (Mikulicz, Bishop-Koop, and Santulli). Post-operative management includes: 10% acetylcysteine p.o., oral feedings (pregestimil), pancreatic enzyme replacement, and prophylactic pulmonary therapy. Long-term prognosis depends on the degree of severity and progression of cystic fibrosis pulmonary disease.
Total colonic aganglionosis (TCA) is found in
approx. 2 to 13% of patients with Hirschsprung's disease (2). There are
three critical phases for patients with TCA (15).
The first period comprises the time from birth until correct diagnosis. Patients with TCA present with a large variety of symptoms. Several authors have outlined the diagnostic problems in patients with TCA (2,4,18). Atypical symptoms may lead to excessively delayed diagnosis. Festen et al. report a delay in diagnosis up to 160 days after birth (4). Patients present with either ileus or symptoms as in typical Hirschsprung's disease but additionally with recurrent vomiting. In patients presenting with ileus, diagnosis may be delayed for several weeks because causative factors like volvulus or meconium ileus do not primarily warrant investigations for aganglionosis. Furthermore, TCA may be associated with other anomalies of the gastrointestinal tract. Only a few reports of TCA associated with small bowel atresia and volvulus can be found (3, 7). Lally et al. report anastomotic failure following repair of ileal atresia due to underlying extensive aganglionosis (11). In cases of midgut volvulus without malrotation, aganglionosis has to be ruled out. Stringer et al. recently published a series of seven full-term infants with meconium ileus due to extensive intestinal aganglionosis (18). Neonatal appendicitis, a very rare disease, may be the leading symptom of TCA. Therefore, rectal biopsies are mandatory in those cases. Ratta et al. state that lack of awareness of the condition may lead to delay in diagnosis and inappropriate treatment (15). Additional to the diagnostic problems due to atypical and heterogenic symptoms, histochemical examination of rectal biopsies may prove negative or equivocal because increased acetylcholinesterase activity may not be present in TCA (5,10,12). Furthermore, there is no typical radiographic pattern (13,17). Plain abdominal radiographs usually suggests low bowel obstruction whereas barium enema usually does not show pathognomonic features.
If no mechanical obstruction is found at laparotomy in neonates presenting with ileus, it is suggested to resect the appendix to rule out TCA. If rectal mucosal biopsies are negative or equivocal, biopsies should be repeated or a formal sphincterectomy for thorough analysis is done.
The second period lasts from the raising of stoma to its closure, including the definite surgical procedure. Failure to thrive and excessive fluid losses have been reported in patients with ileostomies (2). Post-ileostomy complications, however, have been eliminated after the importance of oral sodium supplementation to maintain the enteral co-transport system has been realized (16). In the series of Cass & Myers, ileostomy dysfunction was common with a 20% prolapse rate and 25% rate of persistent excessive losses (2). Interestingly, right transversostomies may show a good function even in cases of TCA. Therefore, frozen section biopsies are mandatory when raising a stoma.
The definitive surgical procedure has been debated (2,5,8,9,15). Colonic patch graft procedures were the first proposals for surgical management of TCA (14). The rational behind were to use the distinctive resorptive function of part of the aganglionic colon (6). Use of the right colon has the theoretical advantage of improved water resorption. However the colon patch procedures have significant complications, e.g., enterocolitis, ulceration of the aganglionic pouch, perforations and extreme dilatation. Multiple modifications of the technique have been reported but none were superior (1,8,9,18). Actually, a modified Duhamel's pull-through procedure seems favorable in the treatment of TCA (2,15).
The third critical phase begins with closure of the stoma. Complications in this period are predominantly recurrent episodes of sub-ileus and diarrhea or nocturnal incontinence. The cause for sub-ileus is a raised tone in the residual sphincter. Repeated manual anal dilatations may be mandatory. The treatment of diarrhea may be managed by diets and/or Loperamide often in large doses. Side effects of large doses of Loperamide are mental irritability and dyskinesia.
Significantly better survival of the patients with TCA nowadays is mainly attributed to more accurate diagnosis and improved management of infants with ileostomies.
1. Boley SJ: A new approach to total aganglionosis of the colon. Surg Gynecol Obstet 159:481-484, 1984
2. Cass DT, Myers N: Total colonic aganglionosis: 30 years' experience. Pediatr Surg Int 2:68-75, 1987
3. Fekete CN, Ricour C, Martelli H: Total colonic aganglionosis (with or without ileal involvement): A review of 27 cases. J Pediatr Surg 21:251-254, 1986
4. Festen C: Total colonic aganglionosis: A diagnostic problem. Z Kinderchir 27:330-337, 1979
5. Festen C, Severijner R, v.d. Staak F: Total colonic aganglionosis: Treatment and follow-up. Z Kinderchir 44:153-155, 1989
6. Heath AL, Spitz L, Milla PJ: The absorptive function of colonic aganglionoic intestine: Are the Duhamel and Martin procedures rational? J Pediatr Surg 20:34-36, 1985
7. Ikeada K, Goto S: Total colonic aganglionosis with or without small bowel involvement: An analysis of 137 patients. J Pediatr Surg 21:319-322, 1986
8. Kimura K, Nishijima E, Muraji T: A new surgical approach to extensive aganglionosis. J Pediatr Surg 16:840-843, 1981
9. Kimura K, Nishijima E, Muraji T: Extensive aganglionosis: Further experience with the colonic patch graft procedure and long-term results. J Pediatr Surg 23:52-56, 1988
10. Kurer MH, Lawson JON, Pambakian H: Suction biopsy in Hirschsprung's disease. Arch Dis Child 61:83-84, 1986
11.Lally KP, Chwals WJ, Weitzman JJ: Hirschsprung's disease: A possible cause of anastomotic failure following repair of intestinal atresia. J Pediatr Surg 27:469-470, 1992
12. Lister J, Tam PKH: Hirschsprung's disease. In: Neonatal Surgery, Hrsg. Lister J, Irving IM, Burrterworth, London, p.523-546, 1990
13. Louw JH: Total colonic aganglionosis. Can J Surg 21:397-405, 1971
14.Martin L: Surgical management of Hirschsprung's disease involving the small intestine. Arch Surg 97:183-189, 1968
15.Ratta BS, Kiely EM, Spitz L: Improvements in the management of total colonic aganglionosis. Pediatr Surg Int 5:30-36, 1990
16. Sacher P, Hirsig J, Gresser J et al: The importance of oral sodium replacement in ileostomy patients. Progr Pediatr Surg 24:226-231, 1989
17. Swenson O, Sherman JO, Fisher JH: Diagnosis of congenital megacolon: an analysis of 501 patients. J Pediatr Surg 7:587-594, 1973
18. Stringer MD, Brereton RJ, Drake DP: Meconium ileus due to extensive intestinal aganglionosis. J Pediatr Surg 29:501-503, 1994
Peter Sacher, MD
Pediatric Surgical Department
University Children's Hospital
anus (IA) is a congenital anomaly in which the natural anal opening is
absent. Diagnosis of IA is usually made shortly after birth on routine
physical examination. The incidence of IA is approximately 1 in
live births and it is more common in males. Its etiology is unknown and
it runs equally through all racial, cultural and socio-economic groups.
There is preliminary evidence (> 5 case reports) of the existence of
inheritance (both dominant and recessive) in patients with anorectal
IA is classified as either "high" or "low" depending on the termination of the distal rectum. When the rectum ends above the levator muscles the malformations are classified as high, and when the rectum ends below the levator muscles the malformations are classified as low. High lesions are more frequent in males, low ones in females. Determination of the level of the lesion (by abdominal x-ray or perineal ultrasound) is critical for appropriate management. Children who have IA may also have other congenital anomalies. The acronym VACTERL describes the associated problems that infants with IA may have: Vertebral defects, Anal atresia, Cardiac anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb anomalies.
Repair of low IA is relatively simple and is usually treated with perineal anoplasty; however, repair of high IA is more complex. Patients are initially given a temporary colostomy and time is given to allow the child to grow. A pull-through operation is completed at a later date. Independent of the level of the lesion, the goal of the surgery is the creation of adequate nerve and muscle structures around the rectum and anus to provide the child with the capacity for bowel control.
MALES: most important decision in the initial management of Imperforate Anus (IA) male patient during the neonatal period is whether the baby needs a colostomy and/or another kind of urinary diversion procedure to prevent sepsis or metabolic derangements. Male patients will benefit from perineal inspection to check for the presence of a fistula (wait 16-24 hours of life before deciding). During this time start antibiotherapy, decompress the GI tract, do a urinalysis to check for meconium cells, and an ultrasound of abdomen to identify urological associated anomalies. Perineal signs in low malformations that will NOT need a colostomy are: meconium in perineum, bucket-handle defect, anal membrane and anal stenosis. These infants can be managed with a perineal anoplasty during the neonatal period with an excellent prognosis. Meconium in urine shows the pt has a fistula between the rectum and the urinary tract. Flat "bottom" or perineum (lack of intergluteal fold), and absence of anal dimple indicates poor muscles and a rather high malformation needing a colostomy. Patients with no clinical signs at 24 hours of birth will need a invertogram or cross-table lateral film in prone position to decide rectal pouch position. Bowel > 1 cm from skin level will need a colostomy, and bowel < 1 cm from skin can be approach perineally. Those cases with high defect are initially managed with a totally diverting colostomy. Diverting the fecal stream reduces the chances of genito-urinary tract contamination and future damage.
FEMALES: most frequent defect in females patient with imperforate anus (IA) is vestibular fistula, followed by vaginal fistulas. In more than 90% of females cases perineal inspection will confirm the diagnosis. These infants require a colostomy before final corrective surgery. The colostomy can be done electively before discharge from the nursery while the GI tract is decompressed by dilatation of the fistulous tract. A single orifice is diagnostic of a persistent cloacal defect usually accompany with a small-looking genitalia. Cloacas are associated to distended vaginas (hydrocolpos) and urologic malformations. This makes a sonogram of abdomen very important in the initial management of these babies for screening of obstructive uropathy (hydronephrosis and hydroureter). Hydrocolpos can cause compressive obstruction of the bladder trigone and interfere with ureteral drainage. Failure to gain weight and frequents episodes of urinary tract infections shows a poorly drained urologic system. A colostomy in cloacas is indicated. 10% of babies will not pass meconium and will develop progressive abdominal distension. Radiological evaluation will be of help along with a diverting colostomy in this cases. Perineal fistulas can be managed with cutback without colostomy during the neonatal period.
The most important prognostic characteristic is the severity of the IA. Patients with low IA have a good probability of having normal stool patterns. Patients with high IA report more problems such as fecal incontinence and constipation. For patients who cannot maintain normal bowel function, the use of a special diet, underpants liners, enemas and drugs have ameliorated their lives. Long-term follow up (with both qualitative and quantitative quality of life considerations) of these patients is very important. In addition, the use of anal endosonography and/or manometry can be used as objective measurements of anorectal pressure and sphincter function.
1- Chen CJ: The treatment of imperforate anus: experience with 108 patients. J Pediatr Surg 34(11):1728-32, 1999.
2- Landau D, Mordechai J, Karplus M, Carmi R: Inheritance of familial congenital isolated anorectal malformations: case reports and review. Am J Med Genetics 71:280-282, 1997.
3- Rintala RJ, Lindahl HG, Rasanen M: Do children with repaired low anorectal malformations have normal bowel function? J Pediatr Surg 32(6):823-826, 1997.
4- Peña A: Anorectal malformations. Semin Pediatr Surg 4(1):35-47, 1995
5- Peña A: Management of anorectal malformations during the newborn period. World J Surg 17(3):385-92, 1993
6- Peña A: Posterior sagittal approach for the correction of anorectal malformations. Adv Surg 19:69-100, 1986
7- Peña A: Surgical treatment of high imperforate anus. World J Surg 9(2):236-43, 1985
8- deVries PA, Peña A: Posterior sagittal anorectoplasty. J Pediatr Surg 17(5):638-43, 1982
Although intussusception can occur at
age, the greatest incidence occurs in infants between 4-10 months of
Over half of the cases are in the first year of life. Frequently occurs
after a recent upper respiratory infection, by Adenovirus type 3 that
a reactive lymphoid hyperplasia that act as lead point (of Peyer's
A definite lead point is identified in about 5% of patients. These include: Meckel's diverticulum, polyps, Henoch's Schonlein purpura, hematoma, lymphoma, foreign bodies, and duplications. Most children have no lead point and it is felt that enlarged mesenteric nodes or swollen Peyer's patches may be the cause. The baby has intermittent periods of severe discomfort with screaming, stiffening and drawing up of the legs, followed by periods of rest. Vomiting may occur and bloody, mucoid (currant jelly) stool may be passed. The baby may become dehydrated and appear acutely ill. Frequently, lethargy may be an early sign. The diagnosis is made by barium enema, and hydrostatic reduction of the intussusception with barium is successful in approximately 50% of cases. To be successful, the barium must reflux into the terminal ileum. The surgeon should be notified before an attempt at barium reduction, and should be present at the time of study. Recently the use of gas enema reduction has been successful in patients with: (1) symptoms less than 12 hours, (2) no rectal bleeding, (3) absence of small bowel obstruction, and (4) normally hydrated. Ultrasonography can be used as a rapid sensitive screening procedure in the initial diagnosis of intussusception. Previous adverse clinical features that precluded barium reduction can be replaced during gas reduction. Predictors of failure of reduction are: (1) ileocolic intussusception, (2) long duration of symptoms, (3) rectal bleeding, and (4) failed reduction at another institution. Air reduction (pneumocolon) is a very effective alternative method since it brings less radiation (shorter flouroscopy time), less costs and less morbidity in cases of perforations.
Failure of hydrostatic reduction requires urgent operation through a right lower quadrant horizontal incision. The intussusception is reduced by pushing on the distal bowel like a tube of toothpaste rather than pulling the proximal bowel. Most cases are ileo-colic intussusception, and a few are jejuno-jejunal or ileo-ileal intussusception.
The traditional method of diagnosing and managing ileo-colic intussusception is barium enema contrast reduction. In China where this is the most common surgical emergency in childhood, pneumatic reduction has been used for more than 25 years. A recent tendency toward this approach is seen in recent years in Occident. This consist of rectal insufflation of oxygen at a flow rate of 2 L/min, controlling pressure by adjusting the height of the mercury column, and using maximal pressures of 80 mm Hg. Small bowel aeration is a sign of complete reduction. Series are successful in 70-90% of cases. Gas enema reduction is very successful in patients with: (1) symptoms less than 12 hours, (2) no rectal
bleeding, (3) absence of small bowel obstruction, and (4) normally hydrated. Ultrasonography can be
used as a rapid sensitive screening procedure in the initial diagnosis of intussusception. Previous
adverse clinical features that precluded barium reduction can be replaced during gas reduction.
Predictors of failure of reduction are: (1) ileocolic intussusception, (2) long duration of symptoms, (3)
rectal bleeding, and (4) failed reduction at another institution. Air reduction (pneumocolon) is a very
effective alternative method since it brings less radiation (shorter flouroscopy time), less costs and less
morbidity in cases of perforations.
Intestinal Neuronal Dysplasia (IND) is a
motility disorder first described in 1971 by Meier-Ruge associated to
histochemical changes of the bowel wall (hyperplasia of submucous &
myenteric plexus with giant ganglia formation, isolated ganglion
cells in lamina propia and muscularis mucosa, elevation of
in parasympathetic fiber of lamina propia and circular muscle, and
plexus sympathetic hypoplastic innervation), also known as
associated to elevated acetylcholinesterase parasympathetic staining.
condition can occur in an isolated form (either localized to colon or
throughout the bowel), or associated to other diseases such as
(HD), neurofibromatosis, MEN type IIB, and anorectal malformations. It
is estimated that 20-75% of HD cases have IND changes proximal to the
segment. Clinically two different types of isolated IND have been
Type A shows symptoms of abdominal distension, enterocolitis, bloody
intestinal spasticity in imaging studies (Ba Enema) since birth, is
common and associated with hypoplasia of sympathetic nerves. Type B is
more frequent, symptoms are indistinguishable from that of HD, with
constipation, megacolon, and repeated episodes of bowel obstruction.
depends on clinical situation; conservative for minor symptoms until
maturation occurs around the 4th year of life, colostomy and
therapy for life threatening situations.
A. Diaphragmatic Hernias
A.1 Congenital Diaphragmatic Hernia (Bochdalek)
The most common congenital diaphragmatic hernia (CDH) is that
occurs through the postero-lateral defect of Bochdalek. It is caused by
failure of the pleuroperitoneal membrane to develop adequately and
before the intestines returning to the abdomen at the tenth week of
The intestines then enter the pleural cavity and cause poor lung
leading to pulmonary hypoplasia (a reduced number of alveoli per area
lung tissue). This defect is postero-lateral in the diaphragm and may
in size. Stomach, liver or spleen may be partly in chest as well.
is 1:2000 live births and the natural history in prenatally diagnosed
is that 60% will die. The clinical presentation is that the newborn
rapidly cyanotic, acidotic, and has poor ventilation. Major findings
to the degree of pulmonary maldevelopment. Chest films will show
in the chest. Left sided hernias are more common than right (90% on
Placement of a radiopaque nasogastric tube may show the tube coiled in
the lower left chest. Higher risk factors are: early appearance of
in life, prematurity and associated anomalies. Treatment consist of
intubation and ventilation with use of muscle relaxants, placement of a
nasogastric tube to prevent gaseous distension of the intestines and
stabilization of arterial blood gases and acid-base status. Surgery can
be undertaken when one of the following objectives are met: (1) blood
normalize with no significant changes between preductal and postductal
samples, (2) echocardiogram demonstrate reduce pulmonary pressure and
Operative management consist of abdominal approach, closure of hernia by primary repair or use of mesh, and correction of malrotation. Postoperative management is very difficult. Due to hypoplastic lungs, there is frequently pulmonary hypertension leading to right-to-left shunting and progressive hypoxemia, hypercarbia, and acidosis that worsens the pulmonary hypertension. The use of chest tubes may cause overstretching of the already hypoplastic alveoli causing: increase pulmonary hypertension, reduce functional residual capacity and reduce lung compliance. Postoperatively, the infant should be kept paralyzed and ventilated and only very slowly weaned from the ventilator. The severity of pulmonary hypoplasia, both ipsilaterally and contralaterally, is the main determinant of outcome. ECMO (extracorporeal membrane oxygenator) has come to reduce somewhat the mortality of this condition.
The mortality of CDH is directly related to the degree of lung hypoplasia associated. Death is caused by persistent pulmonary hypertension and right ventricular failure. Prospective studies of prenatally diagnosed fetus prior to 25 wk. gestation has shown that 60% will die despite optimal postnatal care. This unsolved problem has prompted investigators to develop new treatment options such as preoperative stabilization, jet-frequency ventilation, and ECMO. Another area of development is intrauterine fetal surgical repair. To achieve success fetal surgery should: (1) pose no risk to the mother (innocent bystander) or her future reproductive capacity; (2) tocolytic therapy in the post-op weeks should proved effective to avoid prenatal stillbirths; and (3) the procedure should be superior to conventional therapy. Intrauterine repair has meet with limited success due to herniation of the fetal liver into the chest through the defect. Disturbance of the umbilical circulation during or after liver reduction causes fetal death. Positive-pressure ventilation after birth reduces the liver before the baby comes for surgical repair. Dr. Harrison (USFC Fetal Treatment Center) has devised separate fetal thoraco-abdominal incisions to deal with this problem ("two-step dance"), reducing or amputating the left lateral segment of the liver. Another less invasive approach is enlarging the hypoplastic lungs by reducing the normal egress of fetal lung fluid with controlled tracheal obstruction called PLUGS (Plug Lung Until it Grows).
Delayed presentation beyond the neonatal period is rare, estimated to occur in 4-6% of cases. Infants and children will present with either respiratory or gastrointestinal symptoms such as: chronic respiratory tract infection, vomiting, intermittent intestinal obstruction, and feeding difficulty. Occasionally the child is asymptomatic. The small size of the defect protected by either the spleen or the liver and the presence of a hernial sac may delay the intestinal herniation into the chest. A rise intrabdominal pressure by coughing or vomiting transmitted to any defect of the diaphragm makes visceral herniation more likely. Diagnosis is confirmed by chest or gastrointestinal contrast imaging. Management consists of immediate surgery after preop stabilization. Most defects can be closed primarily through an abdominal approach. Chest-tube placement in the non-hypoplastic lung is of help. Surgical results are generally excellent. A few deaths have resulted from cardiovascular and respiratory compromise due to visceral herniation causing mediastinal and pulmonary compression.
A.2 Morgagni Hernias
First described in 1769, Morgagni Hernias (MH) are rare
diaphragmatic defects close to the
anterior midline between the costal and sternal origin of the diaphragm. They occur retrosternally in the
midline or more commonly on either side (parasternally) of the junction of the embryologic septum
transversum and thoracic wall (see the figure) representing less than 2% of all diaphragmatic defects.
Almost always asymptomatic, typically present in older children or adults with minimal gastrointestinal
symptoms or as incidental finding during routine chest radiography (mass or air-fluid levels). Infants
may develop respiratory symptoms (tachypnea, dyspnea and cyanosis) with distress. Cardiac
tamponade due to protrusion into the pericardial cavity has been reported. The MH defect contains a
sac with liver, small/ large bowel as content. Associated conditions are: heart defects, trisomy 21,
omphalocele, and Cantrells' pentalogy. US and CT-Scan can demonstrate the defect. Management is
operative. Trans-abdominal subcostal approach is preferred with reduction of the defect and suturing of
the diaphragm to undersurface of sternum and posterior rectus sheath. Large defects with phrenic
nerve displacement may need a thoracic approach. Results after surgery rely on associated conditions.
A.3 Esophageal Hernias
Two types of esophageal hernia recognized are the hiatal and
hernia. Diagnosis is
made radiologically always and in a number of patients endoscopically. The hiatal hernia (HH) refers to
herniation of the stomach to the chest through the esophageal hiatus. The lower esophageal sphincter
also moves. It can consist of a small transitory epiphrenic loculation (minor) up to an upside-down
intrathoracic stomach (major). HH generally develops due to a congenital, traumatic or iatrogenic factor.
Most disappear by the age of two years, but all forms of HH can lead to peptic esophagitis from
Gastroesophageal reflux. Repair of HH is determined by the pathology of its associated reflux (causing
failure to thrive, esophagitis, stricture, respiratory symptoms) or the presence of the stomach in the
thoracic cavity. In the paraesophageal hernia (PH) variety the stomach migrates to the chest and the
lower esophageal sphincter stays in its normal anatomic position. PH is a frequent problem after
antireflux operations in patients without posterior crural repair. Small PH can be observed. With an
increase in size or appearance of symptoms (reflux, gastric obstruction, bleeding, infarction or
perforation) the PH should be repaired. The incidence of PH has increased with the advent of the
PROCESUS VAGINALIS REMNANTS
B.1 Inguinal Hernias
A hernia is defined as a protrusion of a portion of an
or tissue through an abnormal opening. For groin (inguinal or femoral)
hernias, this protrusion is into a hernial sac. Whether or not the mere
presence of a hernial sac (or processus vaginalis) constitutes a hernia
is debated. Inguinal hernias in children are almost exclusively
type. Those rare instances of direct inguinal hernia are caused by
surgery and floor disruption. An indirect inguinal hernia protrudes
the internal inguinal ring, within the cremaster fascia, extending down
the spermatic cord for varying distances. The direct hernia protrudes
the posterior wall of the inguinal canal, i.e., medial to deep inferior
epigastric vessels, destroying or stretching the transversalis fascia.
The embryology of indirect inguinal hernia is as follows: the duct
to the testicle is a small offshoot of the great peritoneal sac in the
lower abdomen. During the third month of gestation, the processus
extends down toward the scrotum and follows the chorda gubernaculum
extends from the testicle or the retroperitoneum to the scrotum. During
the seventh month, the testicle descend into the scrotum, where the
vaginalis forms a covering for the testicle and the serous sac in which
it resides. At about the time of birth, the portion of the processus
between the testicle and the abdominal cavity
obliterates, leaving a peritoneal cavity separate from the tunica vaginalis that surrounds the testicle.
Approximately 1-3% of children have a hernia. For infants born prematurely, the incidence varies from 3-5%. The typical patient with an inguinal hernia has an intermittent lump or bulge in the groin, scrotum, or labia noted at times of increased intra-abdominal pressure. A communicating hydrocele is always associated with a hernia. This hydrocele fluctuates in size and is usually larger in ambulatory patients at the end of the day. If a loop of bowel becomes entrapped (incarcerated) in a hernia, the patient develops pain followed by signs of intestinal obstruction. If not reduced, compromised blood supply (strangulation) leads to perforation and peritonitis. Most incarcerated hernias in children can be reduced.
The incidence of inguinal hernia (IH) in premature babies (9-11%) is higher than full-term (3-5%), with a dramatic risk of incarceration (30%). Associated to these episodes of incarceration are chances of: gonadal infarction (the undescended testes complicated by a hernia are more vulnerable to vascular compromise and atrophy), bowel obstruction and strangulation. Symptomatic hernia can complicate the clinical course of babies at NICU ill with hyaline membrane, sepsis, NEC and other conditions needing ventilatory support. Repair should be undertaken before hospital discharge to avoid complications. Prematures have: poorly developed respiratory control center, collapsible rib cage, deficient fatigue-resistant muscular fibers in the diaphragm that predispose then to potential life-threatening post-op respiratory complications such as: need of assisted ventilation (most common), apnea and bradycardia, emesis, cyanosis and re-intubation (due to laryngospasm). Independent risk factors associated to this complications are (1) history of RDS/bronchopulmonary dysplasia, (2) history of patent ductus arteriosus, (3) low absolute weight (< 1.5 Kg), and (4) anemia (Hgb < 10 gm- is associated to a higher incidence of post-op apnea). Postconceptual age (sum of intra- and extrauterine life) has been cited as the factor having greatest impact on post-op complications. These observation makes imperative that preemies (with post conceptual age of less than 45 weeks) be carefully monitored in-hospital for at least 24 hours after surgical repair of their hernias. Outpatient repair is safer for those prematures above the 60 wk. of postconceptual age. The very low birth weight infant with symptomatic hernia can benefit from epidural anesthesia.
At times, the indirect inguinal hernia will extend into the scrotum and can be reduced by external, gentle pressure. Occasionally, the hernia will present as a bulge in the soft tissue overlying the internal ring. It is sometimes difficult to demonstrate and the physician must rely on the patient's history of an intermittent bulge in the groin seen with crying, coughing or straining.
Elective herniorrhaphy at a near convenient time is treatment of choice. Since risk of incarceration is high in children, repair should be undertaken shortly after diagnosis. Simple high ligation of the sac is all that is required. Pediatric patients are allowed to return to full activity immediately after hernia repair. Patients presenting with incarceration should have an attempt at reduction (possible in greater than 98% with experience), and then admission for repair during that hospitalization. Bilateral exploration is done routinely by most experienced pediatric surgeons. Recently the use of groin laparoscopy through the hernial sac permits visualization of the contralateral side.
Approximately 1% of females with inguinal hernias will have the testicular feminization syndrome. Testicular feminization syndrome (TFS) is a genetic form of male pseudohermaphroditism (patient who is genetically 46 XY but has deficient masculinization of external genitalia) caused by complete or partial resistance of end organs to the peripheral effects of androgens. This androgenic insensitivity is caused by a mutation of the gene for androgenic receptor inherited as an X-linked recessive trait. In the complete form the external genitalia appear to be female with a rudimentary vagina, absent uterus and ovaries. The infant may present with inguinal hernias that at surgery may contain testes. Axillary/pubic hair is sparse and primary amenorrhea is present. The incomplete form may represent undervirilized infertile men. Evaluation should include: karyotype, hormonal assays, pelvic ultrasound, urethrovaginogram, gonadal biopsy and labial skin bx for androgen receptor assay. This patients will never menstruate or bear children. Malignant degeneration (germ cell tumors) of the gonads is increased (22-33%). Early gonadectomy is advised to: decrease the possible development of malignancy, avoid the latter psychological trauma to the older child, and eliminate risk of losing the pt during follow-up. Vaginal reconstruction is planned when the patient wishes to be sexually active. These children develop into very normal appearing females that are sterile since no female organs are present.
A hydrocele is a collection of fluid in the space surrounding the testicle between the layers of the tunica vaginalis. Hydroceles can be scrotal, of the cord, abdominal, or a combination of the above. A hydrocele of the cord is the fluid-filled remnant of the processus vaginalis separated from the tunica vaginalis. A communicating hydrocele is one that communicates with the peritoneal cavity by way of a narrow opening into a hernial sac. Hydroceles are common in infants. Some are associated with an inguinal hernia. They are often bilateral, and like hernias, are more common on the right than the left. Most hydroceles will resolved spontaneously by 1-2 years of age. After this time, elective repair can be performed at any time. Operation is done through the groin and search made for an associated hernia. Aspiration of a hydrocele should never be attempted. As a therapeutic measure it is ineffective, and as a diagnostic tool it is a catastrophe if a loop of bowel is entrapped. A possible exception to this is the postoperative recurrent hydrocele.
C. Undescended Testis
The undescended testis is a term we use to
all instances in which the testis cannot be manually manipulated into
scrotum. The testes form from the medial portion of the urogenital
extending from the diaphragm into the pelvis. In arrested descent, they
may be found from the kidneys to the internal inguinal ring. Rapid
through the internal inguinal ring commences at approximately week 28,
the left testis preceding the right. Adequate amounts of male hormones
are necessary for descent. The highest levels of male hormones in the
circulation have been demonstrated at week 28. Thus, it appears that
of descent may be related to inadequate male hormone levels or to
of the end-organ to respond. The undescended testes may be found
from the hilum of the kidney to the external inguinal ring. A patent
vaginalis or true hernial sac will be present 90% of the time.
The undescended testis found in 0.28% of males can be palpable (80%; most at inguinal canal), or
non-palpable (20%). Testes that can be manually brought to the scrotum are retractile and need no
further treatment. Parents should know the objectives, indications and limitations of an orchiopexy: that
the testis could not exist (testicular vanishing syndrome), even after descend can atrophy, that it cannot
be fixed and removal is a therapeutic possibility. To improve spermatogenesis (producing an adequate
number of spermatozoids) surgery should be done before the age of two. Electron microscopy has
confirmed an arrest in spermatogenesis (reduced number of spermatogonias and tubular diameter) in
undescended testis after the first two years of life. Other reasons to pex are: a higher incidence of
malignancy, trauma and torsion, and future cosmetic and psychological problems in the child. The
management is surgical; hormonal (Human Chorionic Gonadotropin) treatment has brought conflicting
results except bilateral cases. Surgery is limited by the length of the testicular artery. Palpable testes
have a better prognosis than non-palpable. Laparoscopy can be of help in non-palpable testis avoiding
exploration of the absent testis.
D. Umbilical Hernias
by: Adrian M. Viens, MS
University of Toronto
An umbilical hernia is a small defect in the abdominal fascial wall in which fluid or abdominal contents protrude through the umbilical ring. The presence of a bulge within the umbilicus is readily palpable and becomes more apparent when the infant cries or during defecation. The actual size of the umbilical hernia is measured by physical examination of the defect in the rectus abdominis muscle, and not by the size of the umbilical bulge. The size of the fascial defect can vary from the width of a fingertip to several centimetres.Embryologically, the cause of an umbilical hernia is related to the incomplete contraction of the umbilical ring. The herniation of the umbilicus is a result of the growing alimentary tract that is unable to fit within the abdominal cavity. Umbilical hernias are more prevalent in females than in males and are more often seen in patients with African heritage. The increased frequency of umbilical hernias has also been attributed to premature babies, twins and infants with long umbilical cords. There is also a frequent association with disorders of mucopolysaccharide metabolism, especially Hurler's Syndrome (gargoylism).Most umbilical hernias are asymptomatic; the decision to repair the umbilical hernia in the first years of life is largely cosmetic and is often performed because of parental request, not because of pain or dysfunction. In the past, some parents use to tape a coin over the umbilical bulge, however, manual compression does not have an effect on the fascial defect.Treatment of umbilical hernia is observation. Most umbilical hernias spontaneously close by age two, with 90% closed by age three and 95% closed by age five. However, surgical repair is recommended if the hernia has not closed by the age of five.If a large defects (> 2cm) remains after the age of 2, spontaneously repair in unlikely and may be closed surgically. The incidence of incarceration (trapped intestinal loop) is rare, even in larger defects. Females should especially have their umbilical hernia corrected before pregnancy because of the associated increased intra-abdominal pressure that could lead to complications. The procedure is simple and incidence of complication such as infection is extremely rare. The repair is usually done as outpatient surgery under general anesthetic.
1-Skandalakis JE, Gray SW (eds): Embryology for surgeons: the embryological basis for treatment of congenital anomalies - 2nd edition. Williams & Wilkins, Baltimore, pp. 563-67, 1994
2- Skinner MA, Grosfeld JL: Inguinal and umbilical hernia repair in infants and children. Surg Clinics of North Am 73(3): 439-49, 1993
3- Raffensperger JG (ed): Swenson's Pediatric Surgery - 5th edition. Appleton & Lange, Norwalk, Connecticut, pp.195, 1990
4- Moore KL: The developing human - 4th edition. Philadelphia, WB Saunders, pp. 231-34, 279-81, 1988
5-Woods GE: Some observations on umbilical hernias in infants. Arch Dis Child 28:450-62, 1953
6- Evans AG: The comparative incidence of umbilical hernias in colored and white infants. J Natl Med Assoc 33:158-60, 1944
The three most common abdominal wall defect in newborns are
hernia, gastroschisis and
omphalocele. Omphalocele is a milder form of primary abdominoschisis since during the embryonic
folding process the outgrowth at the umbilical ring is insufficient (shortage in apoptotic cell death).
Bowel and/or viscera remains in the umbilical cord causing a large abdominal wall defect. Defect may
have liver, spleen, stomach, and bowel in the sac while the abdominal cavity remains underdeveloped in
size. The sac is composed of chorium, Wharton's jelly and peritoneum. The defect is centrally localized
and measures 4-10 cm in diameter. A small defect of less than 2 cm with bowel inside is referred as a
hernia of the umbilical cord. There is a high incidence (30-60%)of associated anomalies in patients with
omphalocele. Epigastric localized omphalocele are associated with sternal and intracardiac defects (i.e.,
Pentalogy of Cantrell), and hypogastric omphalocele have a high association with genito-urinary
defects (i.e., Cloacal Exstrophy). All have malrotation. Cardiac, neurogenic, genitourinary, skeletal and
chromosomal changes and syndromes are the cornerstones of mortality. Antenatal diagnosis may
affect management by stimulating search for associated anomalies and changing the site, mode or
timing of delivery. Cesarean section is warranted in large omphaloceles to avoid liver damage and
dystocia. After initial stabilization management requires consideration of the size of defect, prematurity
and associated anomalies. Primary closure with correction of the malrotation should be attempted
whenever possible. If this is not possible, then a plastic mesh/silastic chimney is fashioned around the
defect to cover the intestinal contents and the contents slowly reduced over 5-14 days. Antibiotics and
nutritional support are mandatory. Manage control centers around sepsis, respiratory status, liver and
bowel dysfunction from increased intraabdominal pressure.
Gastroschisis is a congenital evisceration of part of the
content through an anterior
abdominal wall defect found to the right of the umbilicus. The protruding gut is foreshortened, matted,
thickened and covered with a peel. In a few babies (4 to 23%) an intestinal atresia (IA) further
complicates the pathology. IA complicating gastroschisis may be single or multiple and may involve the
small or large bowel. The IA might be the result of pressure on the bowel from the edge of the defect
(pinching effect) or an intrauterine vascular accident. Rarely, the orifice may be extremely narrow
leading to gangrene or complete midgut atresia. In either case the morbidity and mortality of the child is
duplicated with the presence of an IA. Management remains controversial. Alternatives depend on the
type of closure of the abdominal defect and the severity of the affected bowel. With primary fascial
closure and good-looking bowel primary anastomosis is justified. Placement of a silo calls for delayed
resection performing a second look operation at a later stage to save intestinal length. Angry looking
dilated bowel prompts for proximal diversion, but the higher the enterostomy the greater the problems
of fluid losses, electrolyte imbalances, skin excoriation, sepsis and malnutrition. Closure of the defect
and resection with anastomosis two to four weeks later brings good results. Success or failure is
related to the length of remaining bowel more than the specific method used.
A. Upper GI bleeding (Neonate)
Initially do an Apt test to determine if blood comes from fetal origin or maternal origin (blood swallowed by the fetus). If its of fetal origin then consider a coagulation profile (PT,PTT). If this coagulation profile is normal the possibilities are either stress gastritis or ulcer disease. If the coagulation profile is abnormal then consider hematologic disease of the newborn and manage with vitamin K. The apt test is performed by mixing 1 part of vomitus with 5 part H2O, centrifuge the mixture and remove 5 ml (pink). Then add 1 ml 1% NaOH, wait 2 minutes and if it remains pinks is fetal blood, if it turns brown-yellow its maternal blood.
B. Lower GI bleeding (Neonate)
Again start with an Apt test, if its positive its maternal swallow blood, if its negative do a PT, PTT. If the coagulation profile is abnormal give Vit K for hematologic disorder of newborn. If it's normal do a rectal exam. A fissure could be the cause, if negative then consider either malrotation or Necrotizing enterocolitis.
B.1 Necrotizing Enterocolitis (NEC)
Although the exact pathogenesis of NEC is not known, the most widely held theory is that of perinatal stress leading to selective circulatory ischemia. The stress includes prematurity, sepsis, hypoxia, hypothermia, and jaundice. These babies frequently have umbilical artery, vein catheters, have received exchange transfusions or early feeds with hyperosmolar formulas. The intestinal mucosal cells are highly sensitive to ischemia and mucosal damage leads to bacterial invasion of the intestinal wall. Gas-forming organisms produce pneumatosis intestinalis (air in the bowel wall readily seen on abdominal films). Full-thickness necrosis leads to perforation, free air and abscess formation. These usually premature infants develop increased gastric residuals, abdominal distension, bloody stools, acidosis and dropping platelet count. The abdominal wall becomes reddened and edematous. There may be persistent masses and signs of peritonitis. Perforation leads to further hypoxia, acidosis and temperature instability. The acid-base status is monitored for worsening acidosis and hypoxia. Serial platelet counts are obtained and, with increasing sepsis, the platelet count drops <50,000, indicating intravascular coagulation and decreased bone marrow production. The white blood cell count may be high, low or normal and is not generally of help. Serial abdominal films are obtained to look for evidence of free abdominal air, a worsening picture of pneumatosis intestinalis, or free portal air. Therapy consist initially of stopping feeds, instituting nasogastric suctioning and beginning broad-spectrum antibiotics (ampicillin and gentamycin). Persistent or worsening clinical condition and sepsis or free air on abdominal films require urgent surgical intervention. Attempts to preserve as much viable bowel as possible are mandatory to prevent resultant short gut syndrome.
Complicated NEC is the most common neonatal surgical emergency of modern times, has diverse etiologies, significant mortality and affects mostly premature babies. The use of primary peritoneal drain (PPD) in the management of NEC dates from 1977. The technique is used in the very low birth weight premature infant (<1500 gm) with pneumoperitoneum, metabolic and hemodynamic instability. Consist of a right lower quadrant incision and placement of a drainage (penrose or catheter) under local anesthesia with subsequent irrigation performed bedside at the NICU. Initially used as a temporizing measure before formal laparotomy, some patient went to improvement without the need for further surgery (almost one-third). They either had an immature (fetal type) healing process or a focal perforation (not associated to NEC?) which healed spontaneously. Those babies not improved by PPD either die (20%), go on to laparotomy and half die (20%) or develop complications (24%). Some suggestion made are: PPD should be an adjunct to preop stabilization, before placing drain be sure pt has NEC by X-rays, persistent metabolic acidosis means uncontrolled peritoneal sepsis, do not place drain in pts with inflammatory mass or rapid development of intraperitoneal fluid, the longer the drainage the higher the need for laparotomy.
C. Upper GI Bleeding (Older Children)
In the initial evaluation a history should be obtained for
bleeding disorders, skin lesions, and aspirin or steroid ingestion. The
physical exam for presence of enlarged liver, spleen, masses, ascites,
or evidence of trauma or portal hypertension. Labs such as bleeding
and endoscopy, contrast studies if bleeding stops. Common causes of
GI bleeding are:
(a) Varices- usually presents as severe upper gastrointestinal bleeding in a 2-3 year old who has previously been healthy except for problems in the neonatal period. This is a result of extrahepatic portal obstruction (portal vein thrombosis most commonly), with resulting varices. The bleeding may occur after a period of upper respiratory symptoms and coughing. Management is initially conservative with sedation and bedrest; surgery ir rarely needed.
(b) Esophagitis- this is a result of persistent gastroesophageal reflux leading to inflammation and generally slow, chronic loss of blood from the weeping mucosa. Treatment consist of antacids, frequent small feeds, occasionally medications and if not rapidly improved, then surgical intervention with a fundoplication of the stomach.
(c) Mallory-Weiss- this is a tear of the distal esophagus and/or gastroesophageal junction secondary to severe regurgitation. This was thought to be uncommon in children because it was not looked for by endoscopy. It probably occurs more often than previously thought. Treatment initially is conservative and, if persistent, oversewing of the tear through an incision in the stomach will be successful.
(d) Duplication cysts- Rare cause, they are seen on the mesenteric side of the intestine anywhere from the esophagus to the anus. They bleed when there is ectopic gastric mucosa present. Total excision is curative.
(a) Gastric Erosions- managed medically in most cases.
(b) Ulcer- treated medically unless there is persistent hemorraghe, obstruction or perforation.
(c) Hematoma- usually secondary to trauma or bleeding disorders.
(a) Duodenitis- associated to acid peptic disease.
(b) Hematobilia- secondary to blunt or penetrating abdominal injury. Occasionally requires surgical intervention with local repair or ligation of hepatic vessels.
D. Older GI Bleeding (Older Child)
D.1 Anal Fissure
Anal fissure is the most common cause of rectal bleeding in the
two years of life. Outstretching of
the anal mucocutaneous junction caused by passage of large hard stools during defecation produces a
superficial tear of the mucosa in the posterior midline. Pain with the next bowel movement leads to
constipation, hardened stools that continue to produce cyclic problems. Large fissures with
surrounding bruising should warn against child abuse. Crohn's disease and leukemic infiltration are
other conditions to rule-out. The diagnosis is made after inspection of the anal canal. Chronic fissures
are associated with hypertrophy of the anal papilla or a distal skin tag. Management is directed toward
the associated constipation with stool softeners and anal dilatations, warm perineal baths to relax the
internal muscle spasm, and topical analgesics for pain control. If medical therapy fails excision of the
fissure with lateral sphincterotomy is performed.
D.2 Meckel's Diverticulum
Meckel's diverticulum (MD), the pathologic structure resulting
persistence of the embryonic
vitelline duct (yolk stalk), is the most prevalent congenital anomaly of the GI tract. MD can be the cause
of: gastrointestinal bleeding (most common complication), obstruction, inflammation and umbilical
discharge in children and 50% occur within the first two years of life. Diagnosis depends on clinical
presentation. Rectal bleeding from MD is painless, minimal, recurrent, and can be identified using
99mTc- pertechnetate scan; contrasts studies are unreliable. Persistent bleeding requires arteriography
or laparotomy if the scan is negative. Obstruction secondary to intussusception, herniation or volvulus
presents with findings of fulminant, acute small bowel obstruction, is diagnosed by clinical findings and
contrast enema studies. The MD is seldom diagnosed preop. Diverticulitis or perforation is clinically
indistinguishable from appendicitis. Mucosal polyps or fecal umbilical discharge can be caused by MD.
Overall, complications of Meckel's are managed by simple diverticulectomy or resection with
anastomosis. Laparoscopy can confirm the diagnosis and allow resection of symptomatic cases.
Removal of asymptomatic Meckel's identified incidentally should be considered if upon palpation there
is questionable heterotopic (gastric or pancreatic) mucosa (thick and firm consistency) present.
D.3 Juvenile Polyps
Childhood polyps are usually juvenile (80%). Histology features a
cluster of mucoid lobes surrounded
by flattened mucussecreting glandular cells (mucous retention polyp), no malignant potential.
Commonly seen in children age 310 with a peak at age 56. As a rule only one polyp is present, but
occasionally there are two or three almost always confined to the rectal area (within the reach of the
finger). Most common complaint is bright painless rectal bleeding. Occasionally the polyp may prolapse
through the rectum. Diagnosis is by barium enema, rectal exam, or endoscopy. Removal by endoscopy
is the treatment of choice. Rarely colotomy and excision are required.
A. Wilms Tumor & Genetics
Wilms tumor (WT) is the most common
malignant tumor in children affecting more than 400 children annually
the USA. It has a peak incidence at 3.5 years of age. WT present as a
abdominal or flank mass with abdominal pain, asymptomatic hematuria,
occasionally fever. Other presentations include malaise, weight loss,
left varicocele (obstructed left renal vein), and hypertension. Initial
evaluation consists of: Abdominal films, Ultrasound, IVP, urinalysis,
and Computed Tomography. The presence of a solid, intrarenal mass
intrinsic distortion of the calyceal collecting system is virtually
of Wilms tumor. Doppler sonography of the renal vein and inferior vena
cava can exclude venous tumor involvement. Metastasis occurs most
to lungs and occasionally to liver. Operation is both for treatment and
staging to determine further therapy.
Following NWTSG recommendation's primary nephrectomy is done for all but the largest unilateral tumors and further adjuvant therapy is based on the surgical and pathological findings. Important surgical caveats consist of using a generous transverse incision, performing a radical nephrectomy, exploring the contralateral kidney, avoiding tumor spillage, and sampling suspicious lymph nodes. Nodes are biopsied to determine extent of disease. WT staging by NWTSG consists of:
Stage I- tumor limited to kidney and completely resected.
Stage II- tumor extends beyond the kidney but is completely excised.
Stage III- residual non-hematogenous tumor confined to the abdomen.
Stage IV- hematogenous metastasis.
Stage V- bilateral tumors.
Further treatment with chemotherapy or radiotherapy depends on staging and histology (favorable vs. non-favorable) of the tumor. Non-favorable histologic characteristics are: anaplasia (three times enlarged nucleus, hyperchromatism, mitosis), sarcomatous or rhabdoid degeneration. The success in managing WT has been remarkable the result of stratification, registry and study from the NWTSG. Disease-free survival is 95% for Stage I and approximately 80% for all patients. Prognosis is poor for those children with lymph nodes, lung and liver metastasis.
WT occurs either sporadic (95%), familial (1-2%) or associated with a syndrome (2%). Such syndromes predisposing to WT are WAGR (Wilms, aniridia, genitourinary malformation and mental retardation), Beckwith-Wiedemann Syndrome (gigantism, macroglossia, pancreas cell hyperplasia, BWS), and Denys-Drash Syndrome (male pseudohermaphrodite, nephropathy and Wilms tumor, DDS). They tend to occur in younger patients. Sporadic WT is associated in 10% of cases with isolated hemihypertrophy or genitourinary malformations such as hypospadia, cryptorchidism and renal fusion. Bilateral synchronous kidney tumors are seen in 5-10% of cases. Routine abdominal ultrasound screening every six months up to the age of eight years is recommended for children at high risk for developing WT such as the above-mentioned syndromes.
It was originally thought that WT developed after the two-hit mutational model developed for retinoblastoma: When the first mutation occurs before the union the sperm and egg (constitutional or germline mutation) the tumor is heritable and individuals are at risk for multiple tumors. Nonhereditary WT develops as the result of two-postzygotic mutations (somatic) in a single cell. The two-event hypothesis predicts that susceptible individuals such as familial cases, those with multifocal disease and those with a congenital anomaly have a lower median age at diagnosis than sporadic cases. It is now believed that several genes' mutations are involved in the overall WT pathogenesis.
Loss of whole portions of a chromosome is called loss of heterozygosity (LOH), a mechanism believed to inactivate a tumor-suppressor gene. WT has been found 50% of the time to contain LOH at two genetic loci: 11p13 and 11p15. WT will develop in 30% of WAGR children. Children with the WAGR association shows a deletion in the short arm of chromosome 11 band 13 (11p13) but a normal 11p15 region. Up to a third of sporadic WT have changes in the distal part of chromosome 11, a region that includes band p13. The region of the deletion has been named the WT1 gene, a tumor suppressor gene that also forms a complex with another known tumor-suppressor, p53. WT1 gene express a regulated transcription factor of the zinc-finger family proteins restricted to the genitourinary system, spleen, dorsal mesentery of the intestines, muscles, central nervous system (CNS) and mesothelium. WT1 is deleted in all WAGR syndromes cases. The important association of WT1 mutation and WAGR syndrome with intralobar nephrogenic rests immediately suggest that WT1 expression be necessary for the normal differentiation of nephroblasts. Only five to 10% of sporadic WT have thus far been shown to harbor WT1 mutations. Inactivation of WT1 only affects organs that express this gene such as the kidney and specific cells of the gonads (Sertoli cells of the testis and granulosa cells of the ovary). WT1 has been shown to cause the Denys-Drash syndrome. Most of the mutations described in DDS patients are dominant missense mutations.
A small subset of BWS has a 11p15 duplication or deletion. The region 11p15 has been designated WT2 gene and is telomeric of WT1. Beckwith- Wiedemann form of WT is also associated with IGF2, an embryonal growth-inducing gene. This might prove that two independent loci may be involved in tumor formation. Candidates genes include insulin-like growth factor II gene (IGFII) and the tumor suppressor gene H19. A substantial fraction of WT (without LOH at the DNA level) has been found to have altered imprints with resultants over expression of IGFII and loss of expression of the tumor suppressor H19. IGFII may be operating like an oncogene by perpetuating nephroblast and may account for the perilobar rests observed in BWS patients.
A gene for a familial form (FWT1) of the tumor has also been identified in chromosome 17q. There also might be a gene predisposing to Wilms tumor at chromosome 7p, where constitutional translocations have been described. Mutation in p53 is associated with tumor progression, anaplasia and poor prognosis. Most WT are probably caused by somatic mutations in one or more of the increasing number of WT genes identified.
A few chromosomal regions have seen identified for its role in tumor progression. LOH at chromosome 16q and chromosome 1p has been implicated in progression to a more malignant or aggressive type Wilms' tumor with adverse outcome. This occurs in approximately 20% of patients with WT. These children have a relapse rate three times higher and a mortality rate twelve times higher than WT without LOH at chromosome 1p. p53 is also associated with the so called anaplastic unfavorable histology.
Patients with WT and a diploid DNA content (indicating low proliferation) have been found to have an excellent prognosis. Hyperdiploidy (high mitotic activity) is a poor prognostic feature of Wilms tumor, rhabdomyosarcoma and Osteosarcoma.
Nephrogenic rests are precursor lesions of WT. Two types are recognized: perilobar nephrogenic rests (PLNR) limited to the lobar periphery, and intralobar nephrogenic rests (ILNR) within the lobe, renal sinus or wall of the pelvocaliceal system. The strong association between ILNR, aniridia and Denys-Drash syndrome where the WT1 zinc finger gene has been implicated suggests that this locus might be linked to the pathogenesis of ILNR. Also the association between BWS and some cases of hemihypertrophy with abnormalities of more distant loci on chromosome 11p raises the possibility that the putative WT2 gene might be more closely linked to PLNR.
An advantage of genetic testing is that children with sporadic aniridia, hemihypertrophy or the above discussed syndromes known to be at high risk for developing WT can undergo screening of the germline DNA. This might identify if they harbor the mutation and need closer surveillance for tumor development.
B. Neuroblastoma & Genetics
Neuroblastoma (NB) is the most common
solid tumor in infants. More than 500 new cases are diagnosed annually
in the United States. Most neuroblastomas (75%) arise in the
(adrenal gland and paraspinal ganglia), 20% in the posterior
and 5% in the neck or pelvis. NB is a solid, highly vascular tumor with
a friable pseudocapsule. Most children present with an abdominal mass,
and one-fourth have hypertension. Other have: Horner's syndrome,
eyes, anemia, dancing eyes or vaso-intestinal syndrome. Diagnosis is
with the use of simple X-rays (stipple calcifications), Ultrasound, and
CT-Scan. Work-up should include: bone marrow, bone scan, myelogram (if
there is evidence of intraspinal extension), and plasma/urine tumor
level: vanillylmandelic acid (VMA), homovanillic acid ( HVA) and
Management of NB depends on the stage of disease at diagnosis. Localized tumors are best managed with surgical therapy. Partially resected or unresectable cases need chemotherapy a/o radiotherapy after establishing a histologic diagnosis. Independent variables determining prognosis are age at diagnosis and stage of disease. The Evans classification for NB staging comprised:
Stage I - tumor confined to an organ of origin.
Stage II - tumor extending beyond an organ of origin, but not crossing the midline. Ipsilateral lymph nodes may be involved.
Stage III - tumor extending beyond midline. Bilateral lymph nodes may be involved.
Stage IV - remote disease involving skeleton, bone marrow, soft tissue or distant lymph nodes.
Stage IVS - same as stage I or II with presence of disease in liver, skin or bone marrow.
Young children with stage I/II have a better outcome. A poor outcome is characteristic of higher stages, older patients and those with bone cortex metastasis. Other prognostic variables are: the site of primary tumor development, maturity of tumor, presence of positive lymph nodes, high levels of ferritin, neuron-specific enolase, and diploid DNA.
Neuroblastoma is a malignant tumor of the postganglionic sympathetic system that develops from the neural crest: sympathetic ganglion cells and adrenal gland. In vitro three cell types have been identified:
1- neuroblastic (N-type) cells that are tumorigenic. These cells are responsible for producing cathecolamines and vasoactive substances which help in diagnosis and follow-up therapy.
2- the Schwannian or substrate-adherent (S-type) cells that are non-tumorigenic, and the
3- intermediate I-cells.
NB can behave seemingly benignly and undergo spontaneous regression, mature into a benign ganglioneuroma or most commonly progress to kill its host. This disparate behavior is a manifestation that we are dealing with related tumors with differently genetic and biological features associated with a spectrum of clinical behaviors.
Conclusive associations with environmental factors have not been proved in NB. Hereditary factors are important in NB since a few cases exhibit predisposition following a dominant pattern of inheritance. The most characteristic cytogenetic abnormality of neuroblastoma is deletion of the short arm of chromosome 1 in locus 36 (1p36) occurring in 50 to 70% of primary diploid tumors. LOH of the short arm of chromosome 1 is also associated with an unfavorable outcome, suggesting that a tumor suppression gene may be found in this region. The common region of deletion or LOH resides at the distal end of the short arm of chromosome 1 from 1p36.2 to 1p36.3. Loss or inactivation of a gene at this site is critical for progression of neuroblastoma. A few candidate genes from this site have been mapped. LOH in chromosome 14 long arm (14q) has also been identified in 25-50% or neuroblastoma cells studied but no clinical behavior has been identified with this finding. Gain of chromosome 17 is associated with more aggressive tumors.
Another consistent chromosomal aberration identified in 25 to 30% of NB cells is the presence of double-minute chromosomes, small fragments of chromatin containing multiple copies of the oncogene N-myc produced by amplification. N-myc protooncogene is found on chromosome 2p and its activation results in tumor formation. The amplified N-myc sequence is found on extrachromosomal double minutes (DM) or on homogeneous staining regions (HSR) involving different chromosomes in neuroblastoma (N-type) cell lines. N-myc amplification is strongly associated with advance stages of disease, rapid tumor progression and poor outcome independent of the stage of the tumor or the age of the patient. NB tumors associated with N-myc amplification needs aggressive therapy. N-myc amplification associated with deletion of 1p is correlated with a poor outcome. Deletion of the long arm of chromosome 1 (1q-) is also a poor prognostic sign.
Though most NB cells are diploid, a good number of them are hyperdiploid or triploid. Hyperdiploidy is a good prognostic feature of NB and embryonal rhabdomyosarcoma in infants, while diploid tumors at any age and hyperdiploid in older patients carry a worse prognosis requiring more intensive treatment.
Neuroblast cells needs nerve growth factor (NGF) for proper differentiation. NB tumor cells do not respond to NGF or do not express the receptor. This receptor consists of three transmembrane tyrosine kinase receptors (TRK-A, TRK-B, and TRK-C), known together as the TRK receptor. TRK-A is detected in 90% of NB cells and correlates inversely with N-myc expression. High TRK-A levels correlate strongly with improved survival and plays a role in the propensity for tumors to regress or differentiate into a more benign nature. TRK-B is associated with more matured tumors and TRK-C with lower stage tumors. Alteration in the NGF receptor function or expression promotes tumorigenesis. In conclusion, high levels of TRK expression are associated with better prognosis, earlier stage, lower patient age and lack of N-myc expression.
Neuroblastomas in newborns, cystic tumors, bilateral tumors in infants, and infants less than one year of age with neuroblastoma stage IV-S can undergo neuronal cell differentiation with spontaneous regression. It is thought that high level of TRK-A found in this cases might explain differentiation and regression as high level of this glycoprotein is associated with a favorable prognosis. Regression might be associated with non-affected tumor cell apoptosis.
Other biological markers associated with NB are the multidrug resistance-related protein (MRP) gene, telomerase activity and bcl-2 gene activity. MRP shows a strong correlation with an advanced clinical stages and poor prognosis. High telomerase activity is associated with poor prognosis and high N-myc amplification. The bcl-2 gene produces a protein that prevents neuronal cell death (apoptosis) and promotes tumor progression. Bcl-2 expression is associated with a poor outcome. Apoptosis in NB may result in tumor progression.
The RET proto-oncogene is a protein tyrosine kinase gene (Ret protein) expressed in the cells derived from the neural crest. The activation of RET involves a chromosomal inversion of the long arm of chromosome 10 that juxtaposes the tyrosine kinase encoding domain of RET to the amino terminal sequences of at least three unrelated genes. Germline mutations in the RET gene have been associated with neuroblastoma, pheochromocytoma, multiple endocrine neoplasia (MEN) 2, familial medullary thyroid carcinoma (MTC), radiation-induced thyroid papillary carcinoma, and recently Hirschsprung's disease. RET analysis is a suitable method to detect asymptomatic children with MEN at risk to develop MTC allowing us to consider thyroidectomy at a very early stage of neoplasm development (C-cell hyperplasia) or prophylactically.
High levels of neuron specific enolase and serum ferritin levels are associated with a poor prognosis in NB. Nm-23 and ganglioside GD2 are still other tumor markers associated with poor outcome, active disease and tumor progression.
C. Rhabdomyosarcoma & Genetics
Rhabdomyosarcoma (RMS), the most common
soft tissue sarcoma in infants and children, represents about 5-15% of
all malignant solid lesions. It has a peak incidence before the age of
five years, and a second surge during early adolescence. Head, neck and
pelvic malignancies are more prevalent in infancy and early childhood,
while trunk, extremity and paratesticular sites are largely a disease
adolescents. RMS arises from a primitive cell type and occurs in
tissue at almost any body site excluding brain and bone. The
histologic type in infants and small children is embryonal
occurring in the head and neck, genitourinary tract and
Embryonal RMS is associated with a favorable prognosis. Botryoid RMS is
a subtype of the embryonal variety, which ordinarily extends into body
cavities such as bladder, nasopharynx, vagina, or bile duct. The
cell type, named for a superficial similarity to the pulmonary alveoli,
is the most common form found on the muscle masses of the trunk and
and is seen more frequently in older children and young adults.
RMS is associated with a poor prognosis. This unfavorable prognosis is
the result of early and wide dissemination, bones marrow involvement
poor response to chemotherapy.
Clinical findings, diagnostic evaluation and therapy depend upon location of the primary tumor and are beyond the scope of this review. Head and neck RMS are most common and occur in the orbit, nasopharynx, paranasal sinuses, cheek, neck, middle ear, and larynx. Most are treated by simple biopsy followed by combined therapy or preoperative chemotherapy and radiation followed by conservative resection. Operations for extremity lesions include wide local excision to remove as much of gross tumor as possible. The trend in management is more chemotherapy with conservative surgical therapy. Survival has depended on primary site, stage of disease, and treatment given.
Most RMS occurs sporadically. Approximately 5% are associated to syndromes such as Beckwith-Wiedemann with LOH at the 11p15 locus, Li-Fraumeni, the neurofibromatosis-NF1 gene located on 17q11, Basal Cell Nevus, and the Fetal Alcohol syndrome. Other risk factors in the development of RMS include maternal use of marijuana and cocaine, exposure to radiation, and maternal history of stillbirth.
Alveolar and embryonal RMS are the most genetically studied sarcomas in children. The expression of a number of human paired box-containing (PAX) genes has been correlated with various types of RMS. In alveolar RMS novel fusion genes encoding chimeric fusion proteins have been identified. The most consistent genetic mutation identified in more than 70% of alveolar RMS is translocation of chromosomes 2 and 13, t(2;13)q35-37;q14). The PAX3 loci in chromosome 2 fuses to the FKHR (fork head in rhabdomyosarcoma) domain of chromosome 13 creating a powerful chimeric PAX3-FKHR gene that encodes an 836 amino acid fusion protein. This information is obtained using reverse transcriptase PCR assays of alveolar RMS or by protein immunoprecipitation with PAX3 and FKHR antisera. The PAX3-FKHR protein is an active transcription factor. The t(2;13) activates the oncogenic potential of PAX3 by dysregulating or exaggerating its normal function in the myogenic lineage and affecting the cellular activities of growth, differentiation and apoptosis. Another of the reported translocation is t(1;13)(p36;q14) involving chromosome 1 and 13 in 10% of alveolar RMS. In this variant, Chromosome 1 locus encoding PAX7 fused to FKHR in chromosome 13 resulting in another chimeric transcript PAX7-FKHR. PAX7-FKHR tumors tend to occur in younger patients, are more often in the extremity, are more often localized lesions and are associated with significantly longer event-free survival. Still, a small subset of alveolar RMS does not contain either fusion mutation. The PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status by PCR is a useful diagnostic tool in differentiating RMS from other round cell tumors.
Embryonal RMS contains frequent allelic loss on chromosome 11 (11p15), a genetic feature specific for this type of tumor. Allelic loss is manifested by the absence of one of the two signals in the tumor cells indicating a genetic event such as a chromosome loss, deletion, or mitotic recombination that eliminates one allele and the surrounding chromosomal region. The smallest affected region has been localized to chromosomal region 11p15.5. The presence of a consistent region of allelic loss is often indicative of the presence of a tumor suppressor gene inactivated in the associated malignancy. The mechanism for inactivation of tumor suppressor genes is postulated to be a two-hit scenario in which both copies of the gene are sequentially inactivated: a small point mutation inactivates one of the two alleles, preferably the maternal side allele, and the allelic loss event inactivate the second allele (the paternal allele). This leads to over expression of the insulin-like growth factor II gene known to play a role in the development of embryonal tumors.
Other alterations associated with embryonal RMS are distinct patterns of chromosomal gains (chromosomes 2,7,8,12,13,17,18, and 19) in contrast with alveolar RMS which shows genomic amplification of chromosomal region 12q13-15 in 50% of cases. Notably, these distinct changes predominantly involved chromosomes 2, 12, and 13 in both subtypes. Additionally embryonal RMS cases shows mutations of members of the RAS gene family, a second proto-oncogene. Both tumors share alterations in the p53 gene at the germline level contributing to increase susceptibility to other tumors characteristics of the Li-Fraumeni syndrome. There is also greater over expression of c-myc in alveolar RMS when compared with embryonal RMS. All this favors a multi-step origin of RMS tumors generating phenotypic changes of growth autonomy, abnormal differentiation and motility.
The Li-Fraumeni familial cancer syndrome is manifested by increased susceptibility of affected relatives to develop a diverse set of malignancies during early childhood. The major features of the syndrome include breast cancer, osteosarcoma, rhabdomyosarcomas of soft tissue, glioblastoma, leukemia and adrenal cortical carcinoma. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. Among females, breast cancer is the most common. Germline mutations within a defined region of the p53 gene have been found in families with the Li-Fraumeni syndrome. Persistence of the mutation in the germline suggests a defect in DNA repair in the family member first affected. Asymptomatic carriers of p53 germline mutation needs closed evaluation and follow-up for early detection and treatment in case neoplasia develops.
D. Hepatic Tumors: Hepatoblastoma
Hepatoblastoma (HB) is the most common primary malignant neoplasm
of the liver in children mostly
seen in males less than four year of age. Diagnostic work-up (US, Scintigraphy, CT-Scan) objective is
predicting resectability and tumor extension. Diagnostic laparotomy will decide resectability. Markers
associated to this tumor are: alpha-fetoprotein and gamma-glutamyltransferase II. Only reliable chances
of cure is surgical excision although half are unresectable at dx. Unresectable tumors can be managed
with preop chemotx. Disadvantages of preop chemotx are: progressive disease, increase morbidity,
post-op complications, and toxicity. Advantages are: decrease in tumor size, covert three-fourth cases
into resectable, although extent of surgery is not decreased. Tumor necrosis is more extensive in pt.
receiving preop chemotx. Osteoid present in tumors after chemotx may represent an inherent ability of
the tumor to maturate and differentiate. Diploid tumors on DNA flow cytometry show a better prognosis.
E. Sacrococcygeal Teratoma
Sacrococcygeal teratoma (SCT) is the most common extragonadal
cell tumor in neonates with an
incidence of one in 30-40,000 live births. Three-fourth are females. SCT present as a large, firm or more
commonly cystic masses that arise from the anterior surface of the sacrum or coccyx, protruding and
forming a large external mass. Histology consist of tissue from the three germ cell layers. SCT is
classified as: mature, immature, or malignant (endodermal sinus) and produces alpha-feto protein (AFP).
Prenatal sonographic diagnostic severity criteria are: tumor size greater than the biparietal diameter of
the fetus, rapid tumor growth, development of placentomegaly, polyhydramnios and hydrops. Large
tumors should benefit from cesarean section to avoid dystocia or tumor rupture. Management consist of
total tumor resection with coccyx (recurrence is associated with leaving coccyx in place). Every
recurrence of SCT should be regarded as potentially malignant. Malignant or immature SCT with
elevated AFP after surgical resection will benefit from adjuvant chemotherapy. Survival is 95% for
mature/immature tumors, but less than 80% for malignant cases. Follow-up should consist of (1)
meticulous physical exam every 3-6 months for first three years, (2) serial AFP determination, (3)
fecal/urodynamic functional studies. Long term F/U has found a 40% incidence of fecal and urinary
impairment associated to either tumor compression of pelvic structures or surgical trauma.
F. Ovarian Tumors
Ovarian tumors are uncommon childhood malignancies (1%)
by recurrence and
resistance to therapy. Aggressive surgery is limited to avoid compromising reproductive capacity and
endocrine function. Low incidence and need of mulitinodal therapy encourages referral to centers
dealing with effective cancer therapy.The most common histology is germ cell: dysgerminoma,
teratoma, and endodermal sinus tumor. This is followed by the sex-cord stroma tumors with a low
incidence of malignancy. They can cause feminization (granulosa-theca cell) and masculinization
(androblastoma). Other types are: epithelial (older adolescent), lipid-cell, and gonadoblastoma. Ovarian
tumors present with acute abdominal symptoms (pain) from impending rupture or torsion. They also
cause painless abdominal enlargement, or hormonal changes. Preop work-up should include: human
chorionic gonadotropin (HCG) and alpha-fetoprotein ( AFP) levels. Imaging studies: Ultrasound and
CT-Scan. The most important prognostic factor in malignant tumors is stage of disease at time of
diagnosis. Objectives of surgery are: accurate staging (inspection of peritoneal surfaces and pelvic
organs, lymph node evaluation), washing and cytology of peritoneal fluid, tumor removal, and
contralateral ovarian biopsy if needed. Chemotherapy consists of: bleomycin, cis-platinum, and
vinblastine. Radiotherapy is generally not effective, except in dysgerminoma. Elevation of tumor
markers (AFP or HCG) after therapy signals recurrence.
G. Thyroid Nodules
The need to differentiate malignant from
thyroid nodules is the most challenging predicament in
diagnostic work-up consists of ultrasonography (US), radionuclear scans
(RNS) and fine-needle aspiration biopsy (FNAB). After reviewing our
experience with twenty-four pediatric thyroid nodules we found nineteen
benign and five malignant lesions. Benign nodules were soft, movable,
and non-tender. Malignant nodules were found during late adolecence,
by localized tenderness, a multigandular appearance and fixation to
tissues. US and RNS were of limited utility since malignancy was
among cystic and hot nodules respectively. Suppressive thyroid hormone
therapy was useless in the few cases tried. FNAB in
eighteen cases did not limit the number of thyroid resections. It showed that the probability that a
malignant nodule had suspicious or frankly malignant cytology was 60%. The specificity was 90%. This
is the result of a higher number of patients with follicular cell cytology in the aspirate. No attempts
should be made to differentiate follicular adenoma from carcinoma since capsular and vascular invasion
cannot be adequately assessed by FNAB.The physical exam findings, persistence of the nodule,
progressive growth and cosmetic appearance were the main indications for surgery. FNAB is a safe
procedure that plays a minor role in the decision to withhold surgery. Its greatest strength is to
anticipate in case of malignancy that a more radical procedure is probably needed. FNAB, US and RNS
should not replace clinical judgement or suspicion as the most important determinants in management.
In spite of presenting with advanced, multicentric and larger tumors children have a better survival than adults. Populations at risk: past radiation to head and neck, nuclear waste radiation, MEN II kindred. Clinical presentation is a solitary cervical mass or metastatic lymph node. Diagnostic work-up should include: sonogram (cystic or solid), thyroid scan (cold or hot), Fine-needle aspiration cytology(FNA), and Chest-X-Ray (lung metastasis 20% at dx). Pathology of tumors: papillary (majority, psammomas bodies), follicular (vascular or capsular invasion), medullary (arise from C-cells, multicentric, locally invasive), anaplastic (rare, invasive and metastatic). Management is surgical. Complications of surgery increase with decreasing age of patient: temporary hypoparathyroidism, recurrent nerve injury. Prognostic factors associated to higher mortality are: non-diploid DNA, psammomas bodies, over 2 cm diameter nodule, and anaplastic histology. Follow-up for recurrence with serum thyroglobulin level and radioisotope scans. Adjunctive therapy: thyroid suppression and radio-iodine for lymph nodes and pulmonary metastasis.
H. Burkitt's Lymphoma
Burkitt's lymphoma (BL) is a highly malignant tumor first described during the late 50's in African children (jaw), endemic in nature, and composed of undifferentiated lympho-reticular cells with uniform appearance. The American BL variety is non-endemic, mostly attacks children between 8-12 years of age, predominantly (>75%) with abdominal disease such as unexplained mass, pain, or intussusception. The head and neck region follows. The tumor can appear as a localized, diffuse (multifocal, non-resectable) or metastatic abdominal mass (bone marrow and CNS). It's considered the fastest growing tumor in humans with a doubling time around 12-24 hrs. Chemotherapy is the primary treatment modality due to its effectiveness in rapidly proliferating cells. The role of surgery is to establish the diagnosis (using open biopsy), stage the tumor, remove localized disease, relieve intestinal obstruction and provide vascular access. Complete resection whenever possible offers the patient improved survival. Is more readily accomplished in patients with localized bowel involvement operated on an emergency basis due to acute abdominal symptoms. The only predictor of event free survival is extent of abdominal disease at diagnosis. Debulking (cytoreductive) procedures increases morbidity and delays initiation of chemotherapy worsening prognosis. Extensive tumors should be managed with minimal procedure and immediate chemotherapy (a/o radiotherapy). Bone marrow and CNS involvement are ominous prognostic signs.