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Endoscopic Retrograde Cholangiopancreatograpy (ERCP) in the Evaluation and Management of Abdominal Pain in Children: Experience From a Tertiary Care Center Raj Santharam, Adrian Miranda, Steven Werlin, Kulwinder Dua Introduction: Previous studies have shown ERCP to be feasible and safe in the pediatric population. Aim: To determine the utility of ERCP in the diagnosis and management of abdominal pain in children. Methods: Children (%18 years) undergoing ERCP for evaluation of abdominal pain at one tertiary care center (1996-2003) were identified using an endoscopy database and retrospectively studied. Abdominal pain suggestive of pancreatobiliary origin was classified as Type I if associated with abnormal liver tests and/or abnormal pancreatic enzymes. Those with abdominal pain alone were classified as Type II. Datasets with regard to technical success, outcomes and complications were evaluated. Results: A total of 146 children, (age n: !1 yr, 7; 1 to 12 yrs, 79; 13 to 18yrs, 60) underwent 185 ERCP’s. There were 97 children with type I pain and 49 patients with type II pain. Technical success, as defined by successful papillary cannulation with therapeutic interventions where required, was achieved in 182 of 185 ERCP’s (98%). The diagnostic and therapeutic utility of ERCP in the individual categories of pain is shown in the Table 1. Post-ERCP complications were encountered in 2.1% of patients, none of which required hospitalization beyond one week. There were no procedure related mortalities. Conclusions: ERCP in children is safe and can be performed with high success rates. In addition to the high utility of ERCP in the diagnosis and management of abdominal pain in children with abnormal liver and/ or pancreatic tests, ERCP was also found helpful in over 50% of those with abdominal pain alone.

Most patients are fasted for at least 12 to 24 hours following percutaneous endoscopic gastrostomy. In order to decrease the period of fasting, inadequate nutritional support, and hospitalization time, we began enteral feedings in 24 of 28 consecutive children, aged 4 weeks to 20 years, who were referred for PEG, 6 hours following the procedure. All patients received their full volume of feedings within 24 hours. Twelve of 13 outpatients were discharged in less than 24 hours. There were no complications related to early feeding and no complications that required discontinuation of feedings. Early feeding following PEG insertion is safe in children. (Gastrointest Endosc1994;40:692-3.)

Nineteen children with "severe" colitis (14 with ulcerative colitis and 5 with Crohn's colitis) were analyzed according to newly established criteria. There were 8 boys and 11 girls (mean age 12.3 ± 3.8 years), and duration of acute illness ranged from 2 to 56 days at the time of presentation. Six episodes responded to medical management within 12 days; one episode responded at 3 weeks, one at 4 weeks, and one had not responded when the patient was lost to follow-up. Extending the period of medical treatment beyond 12 days substantially increased morbidity and complications of therapy. No combination of criteria accurately predicted those patients who would respond to medical therapy alone. Ten episodes unresponsive to medical treatment required surgery for control of disease. Of the group who had responded to medical therapy, 5 of the 9 patients required proctocolectomy for intractable disease in the 2-year period after the severe attack, 3 others are doing poorly on a medical regimen (1.5-2.5 years later), and only 1 is in remission (5 years after the severe attack). The data demonstrate that 32% of children with severe colitis had a rapid response to medical management, but the remission achieved was short-lived. The majority of pediatric patients with severe colitis require surgery within 2 years of the onset of the attack.

We investigated myoelectric activity in an 8-month-old male who presented with a perinatal bowel obstruction, duodenal band, congenital short small intestine, and persistent feeding intolerance. Serosal electrodes were surgically implanted on stomach, duodenum, and jejunum during Nissen fundoplication and ileostomy. A 5-cm ileal specimen was taken for in vitro studies. Spontaneous migrating myoelectric complexes (MMC) were present in stomach and small intestine. Bethanechol increased electrical response activity (ERA) in stomach and duodenum. Morphine induced intense ERA and distinct phase III activity. Pentagastrin infusion did not disrupt MMC cycling. Feeding disrupted MMC complex cycling 30-40 min after the meal. Metoclopramide before feeding delayed disruption of the MMC cycling after the feeding. Intermittent gastric arrhythmias were present after the fifth postoperative day. In vitro muscle strips showed spontaneous contractions and electrical control activity (ECA). Bethanechol, McNeil A-343, motilin, and cholecystokinin induced contractions, but pentagastrin had no effect. We conclude that in spite of a major clinical motility dysfunction, several of our findings were normal. The abnormalities include short MMC period, absence of disruption of MMC by pentagastrin, and gastric arrhythmias.

Three children with surgically corrected extrahepatic biliary atresia developed recurrent cholangitis associated with bile lakes that failed to drain via the hepatoportoenterostomy. Surgical or percutaneous drainage of these cysts was followed by both resolution of the infection and spontaneous internal drainage. We postulate that the ongoing inflammatory process resulted in intrahepatic biliary obstruction, which caused cholangitis and bile cysts. Successful treatment required not only antibiotics but drainage of the bile lakes. Development of bile cysts is a new cause of recurrent cholangitis seen in extrahepatic biliary atresia.

Seven children with Crohn's disease and linear growth retardation were studied in order to determine the best method of treating this psychologically debilitating complication. No single therapeutic approach was successful in all patients. Three patients responded to enteral caloric supplementation, one to central venous alimentation, and one low dose corticosteroid therapy, and two responded to surgical extirpation of the involved segments of bowel.

Two new pediatric examples of Caroli disease are reported; one was diagnosed by operative cholangiography and one by percutaneous transhepatic cholangiography. Although a variety of approaches may lead one to suspect the diagnosis, percutaneous transhepatic cholangiography is now the method of choice to establish the diagnosis.

We evaluated by electron microscopy the effects of two hormones, cholecystokinin octapeptide (CCK-8) and hydrocortisone, on the development of the pancreatic acinar cell in newborn rats. The newborn rat pancreas contains abundant zymogen granules of variable size but is unresponsive to secretagogues. In contrast the 24-hr-old pancreas is depleted of granules, indicating emptying of the acinocytes in response to feeding. Zymogen granule content is moderate in the 24-hr-old rat that is fasted from birth. The pancreas from the 24-hr-old rat that is fasted and treated with either hydrocortisone or CCK-8 has an intermediate number of granules. In the animals fasted and treated with hormones, the rough endoplasmic reticulum is arranged into parallel lamellae suggesting a higher level of protein synthesis which may contribute to the formation of abundant zymogen stores. We conclude that zymogen stores are lost earlier postnatally than previously understood, and that zymogen seen in the 24-hr-old animals may represent newly synthesized materials.

Hydrocortisone and cholecystokinin-octapeptide (CCK-8) were injected into newborn rats on days 1-5 of life. Both agents induced significant increases in pancreatic weight, protein, DNA, and specific activities of amylase, chymotrypsinogen, and lipase. The ability of the pancreas to secrete amylase in response to carbachol was decreased by the administration of hydrocorticosterone at age 7 days. CCK-8 increased basal secretion at 7 days. We conclude that growth and secretory capacity of the newborn rat pancreas are under the control of both glucocorticoids and cholecystokinin.

Top of pageAbstract ABSTRACT: To define developmental patterns, we determined the rate of protein and DNA synthesis in rat pancreas at birth, 1, 2, 3, 7, 10, 14, 21, 28 days, 2 months, 3 months, and in adults. Fragments of freshly minced pancreas were incubated with [3H]-thymidine and [14C]-leucine and the DNA and protein synthesis rates were measured. We found that 1) DNA content was lowest at birth, rose through day 3, plateaued at about 8 mg/g wet weight through day 14, then slowly decreased to the adult value of about 5 mg/g at 2 months; 2) protein content, although high at birth, decreased rapidly to a value of 80 mg/g at day 3 and slowly rose to the adult value of 160 mg/g; 3) protein synthesis, low at birth, rapidly increased to about five times the adult value by day 3, and remained elevated for the 1st month; 4) DNA synthesis was 15 times the adult rate at birth, increased to 30 times at 3 days of age, then declined slowly in an exponential fashion to the adult value. We conclude that the pancreas at birth is poised biosynthetically to undergo a rapid hyperplastic and hypertrophic response, and this process reaches a maximal rate at about 3 days of age.

A 5-year-old girl presented with chronic bloody diarrhea. Evaluation including sigmoidoscopy, rectal biopsy, and barium enema was consistent with the diagnosis of ulcerative colitis. Culture of the stool grew Aeromonas hydrophila. A. hydrophila colitis may be more common than presently realized.

Wilson's disease, an autosomal recessive disorder of copper metabolism, may defy diagnosis in children The classical triad of Kayser-Fleischer rings, neurologic dysfunction, and hypoceruloplasminemia may be absent. Patients may be seen initially with acute or chronic hepatitis, hemolytic anemia, or neurologic dysfunction. Guidelines are presented for diagnosis of Wilson's disease based on a review of 25 pediatric and adolescent patients. A high index of suspicion is necessary so that therapy with penicillamine may be begun before irreversible liver or neurologic damage occurs. The prognosis is excellent when diagnosis and treatment are established early.

In order to investigate the mechanisms of severe growth failure in children with Crohn's disease, 7 affected patients (ages 9–17 yr) were studied before, during, and after parenteral nutrition as a supplement to oral intake. At the time of entrance into the study, patients had had cessation of linear growth for at least 1 yr, or a decrease of one standard deviation in height percentiles and/or a bone-age delay greater than 2 yr. Nutritional status was evaluated in all patients, and endocrinologic and metabolic balance studies were performed in 5 of the 7 pa tients. Neither endocrine dysfunction nor malabsorption accounted for the severe growth failure. Patients received approximately 8 wk of combined oral and parenteral nutrition achieving at least 75 calories per kilogram per day or greater. Weight gain averaged 4.8 ± 1.6 kg, while total body potassium (indicative of lean body mass) demonstrated a parallel significant rise (P

A patient with chronic granulomatous disease developed a form of colitis similar to but nearly indistinguishable from Crohn's disease. After initial response to sulfasalazine and prednisone, he became refractory to medical management. Response to total proctocolectomy and ileostomy was dramatic.

Gallbladder disease is known to be increased in sickle cell disease (SS). The prevalence of cholelithiasis in children with SS has been reported as 10% to 37%. Gallbladder ultrasound, cholecystography, and/or abdominal radiography were used to evaluate 31 patients aged 2 to 18 years with no systematic evidence of gallbladder disease for cholelithiasis. Overall prevalence of gallstones was found to be 29%. Cholelithiasis was detected in children as young as 4 years of age. Prevalence below the age of 10 years and above the age of 10 years was found to be 11% and 55% respectively. The increased prevalence of cholelithiasis in children with sickle cell disease suggests the use of diagnostic ultrasonography as a routine screening procedure.

An infant girl with the megacystis microcolon intestinal hypoperistalsis syndrome is reported. The presence of polyhydramnios and the absence of upper urinary tract abnormalities, differentiate this patient from similar cases previously reported. Although the etiology of this disease is unknown, partial success with the use of bethanechol suggests that the deranged intestinal motility may be related to dysfunction of the autonomic nerve endings of the gut.

2. Pollock HM, and Dahlgren BJ: Distribution of streptococcal groups in clinical specimens in evaluation of bacitracin screening, Appl Microbiol 27:I41, 1974. 3. Sprunt K, Vail D, and Asnes RS: Identification of streptococcus pyogenes in a pediatric outpatient department, Pediatrics 54:718, 1974. 4. Murray PR, Wold AD, Hall MH, and Washington JA: Bacitracin differentiation for presumptive identification of 5.

This is a report of a new case of glucose intolerance that developed in a young child with Hirschprung's disease.

In order to determine the spectrum of esophageal dysfunction in repaired esophageal atresia, 14 patients were evaluated with esophageal manometry, intraluminal pH recording, and radiology. Nine patients had no difficulty in swallowing but six had symptoms suggestive of gastroesophageal (GE) reflux. On pH recording, six had evidence of GE reflux. Basal sphincter pressure was 22 mm Hg in both reflux and nonreflux patients. No patient had manometric evidence of peristalsis in the proximal esophagus, but six had peristalsis in the distal esophagus. On radiology all had a normal peristaltic stripping wave in the cervical esophagus, and peristalsis was absent in the proximal thoracic esophagus in all patients but present in the distal esophagus in five of the 10 patients studied. Esophageal dysfunction is present in all patients with repaired esophageal atresia even when symptoms are absent.

Since the fetal alcohol syndrome (FAS) was first described in 1973, 1 a variety of associated anomalies have been reported. We discuss a case of FAS with associated extrahepatic biliary atresia and renal anomalies. Report of a Case. —A 1,450-g girl was born to a 35-year-old mother after a 35-week gestation. The pregnancy was complicated by heavy alcohol ingestion, ranging from six to 12 drinks per day. A previous pregnancy six years earlier had resulted in a normal delivery and healthy older sibling. The diagnosis of FAS was made on the basis of the history and classic clinical features. At 24 hours of age, the patient was noted to be jaundiced, and phototherapy was begun. Laboratory evaluation in the neonatal period included a negative Coombs' test and negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) tests. At 11 weeks of age, she was transferred to Milwaukee

Six adults with myotonic dystrophy underwent detailed radiological and manometric studies of pharyngoesophageal function. Four of the patients had no history of swallowing dysfunction, while two had very mild symptoms. All patients showed abnormalities of pharyngoesophageal function. Pharyngeal peristalsis was present but of low amplitude. Resting upper esophageal sphincter pressure was diminished, but the sphincter relaxed normally. Peristalsis in the esophageal body was in variably absent in the striated muscle segment of the esophagus and was either absent or decreased in amplitude in the smooth muscle segment. The lower esophageal sphincter was normal. Myotonia did not occur in the sphincters or the esophageal body. These findings suggest that phyaryngoesophageal dysfunction is common in patients with myotonic dystrophy, even when clinical symptoms are absent. The abnormalities are probably related to muscle weakness rather than to myotonia in the pharyngeal and esophageal musculature.

Hepatic hypoperfusion can result in ischemic hepatitis, a clinical syndrome characterized by a sudden rise in serum transaminases followed by resolution to near normal levels within 7 to 10 days. Although described in adults, this syndrome has not been well defined in pediatric patients. We report 22 children who developed ischemic hepatitis during an acute illness. Fifteen of 22 patients had a documented hypotensive episode or no cardiac output before the onset of the ischemic hepatitis episode. Four of the seven patients without documented hypotension required pressor therapy to maintain their BP. SGOT showed a marked rise (mean 2294 IU/L, range 438 to 6652) from admission to 96 h (mean 34) with a rapid decline to near normal levels within 9 days (mean 5.1). Serum bilirubin levels also rose transiently, but generally not to the extent of transaminase levels. A clinically significant coagulopathy occurred in six patients. Although nine patients expired, none died as a direct result of the hepatic damage. Ischemic hepatitis can occur during illnesses associated with diminished hepatic blood flow and follows a characteristic course that usually can be differentiated from viral or drug-induced hepatitis on clinical and biochemical criteria.

We studied the lower esophageal sphincter in 29 children with known or suspected gastroesophageal reflux using a sleeve sensor and micro pH electrode. Mean lower esophageal sphincter pressure for a ten-minute monitoring period was 19 +/- 13 mm Hg; however, considerable temporal variation occurred in each child. Gastroesophageal reflex was infrequently associated with a low basal sphincter pressure (5 mm Hg) but usually associated with an increase in intra-abdominal pressure or with transient inappropriate relaxation of the lower esophageal sphincter.

To define the developmental pattern of the trophic effects of cholecystokinin octapeptide (CCK-8) and hydrocortisone on immature rat pancreas, we injected newborn rats, rats aged 4, 7, 11, 18, and 25 days and 3 months, and adult rats with CCK (5 and 10 micrograms/kg) in gelatin and hydrocortisone (10 mg/kg) for 3 days. Animals were killed, the pancreata were removed, and the concentrations of DNA and protein were measured and DNA and protein synthesis rates determined by incorporation of [3H]thymidine and [14C]leucine, respectively. These values were compared with those of saline-injected controls. DNA concentration was significantly increased over control at ages 2 days to adult by hydrocortisone and by CCK (10 micrograms/kg) in the adult. Protein concentration was increased on days 3-14 by hydrocortisone. DNA synthesis was increased by CCK and decreased by hydrocortisone at 3 months and adult. Protein synthesis was decreased by hydrocortisone at ages 3-14 days. Thus, each agent has its own developmental pattern with age on the rat pancreas.

Mechanisms and development of secretory function were studied in rat pancreas in vitro. Amylase release from term fetal pancreas was refractory to stimulation by carbamylcholine chloride (carbachol) and cholecystokinin-octapeptide (CCK-OP), but was significantly augmented by calcium ionophore (A23187), DBcAMP, 8-Br-cGMP, and theophylline. The latter agent when combined with either cyclic nucleotide analogue further increased secretory responses. At 1 day and 8 days postnatally, responsiveness to carbachol and CCK-OP had been acquired because amylase secretion stimulated by these agents was brisk and at a level comparable to that found in mature tissue. Increasing extracellular calcium concentrations from 1.23 to 5.28 mM had no effect on basal amylase release in either the fetal or 8-day pancreas. No changes in intracellular cAMP concentrations were found at any age under experimental conditions used. Similarily, in fetal tissue, no changes in cGMP concentrations were found in response to carbachol or A23187. However, at 8 days of age, both agents produced two- to four-fold increases in tissue cGMP levels at 1, 2, and 5 min of incubation. These studies confirm that responsiveness to carbachol and CCK-OP is a maturational process in the pancreas that lags behind the development of intracellular processes involved in stimulus-secretion coupling.

The authors observed unusually marked involvement of the colon in a patient with chronic granulomatous disease of childhood.

Methotrexate (MTX) and 6-mercaptopurine (6MP), the two drugs most commonly used for maintenance treatment of childhood leukemia, are both potent hepatotoxins. In order to assess MTX-6MP-induced damage, we obtained biopsies from 11 children with acute lymphocytic leukemia (ALL) for light microscopic and transmission electron microscopic study. Prednisone, vincristine, and L-asparaginase were used for induction of remission in all patients. Although light microscopic findings were minimal, we found significant ultrastructural abnormalities in all patients. Changes included nuclear abnormalities, disruption of rough and smooth endoplasmic reticulum, a variety of mitochondrial changes, steatosis, fibrosis, and changes in peroxisomes and lysosomes. These abnormalities could not have been predicted from liver function tests or histopathology. Three of the eleven patients studied had also received cyclophosphamide and cytosine arabinoside during maintenance therapy. The ultrastructural abnormalities in this group were not distinguishable from those observed in the group that did not receive these additional chemotherapeutic agents. The long-term clinical significance of these findings is not known.

Summary: In contrast to morphologic maturity, the newborn rat pancreas is unresponsive to carbachol. At 24 h, carbachol-stimulated secretion of exportable proteins markedly increases. Responsiveness to the calcium ionophore, A23187, is present at term. At age 24 h, pancreas from fasted newborn rats is also unresponsive to carbachol. When cholecystokinin octapeptide or hydrocortisone was administered to fasted newborn rats secretory function developed normally. Thus, responsiveness of newborn rat pancreas to secretagogues matures rapidly and can be induced by hormones. Speculation: When either cholecystokinin octapeptide or hydrocortisone is administered to fasted newborn rats, normal maturation of in vitro secretory function occurs. The actions of these exogenous agents may mimic endogenous release stimulated by first feeding.

Mechanisms and development of pancreas and pancreatic secretory function were studied in the rat. Injections of cholecystokinin octapeptide and hydrocortisone into pregnant rats altered pancreatic size, zymogen enzyme, and DNA content in the fetal newborn pancreas. These studies suggest that the developmental signals for pancreatic function may be related to endogenous release of cholecystokinin or hydrocortisone in the perinatal period.

The ultrastructural pathology of nerve and muscle and the neurological dysfunction in children with cholestatic liver disease and vitamin E deficiency have not been previously correlated. We studied two children with this syndrome. One child, 11 years of age, had severe hyporeflexia and decreased vibratory sense. Nerve conduction was delayed. The second child, 2 years of age, was neurologically normal. Both children showed ultrastructural evidence of damage to the sural nerve and accumulation of electron-dense deposits in the muscle fibers. Abnormalities of the nerves included disruption of the myelin sheath and separation and degeneration of the inner and outer components of the Schmidt-Lanterman incisure.

Isolated acini were prepared from the pancreas of immature rats (age less than 1 hr. - 48 hrs) in order to study the development of the secretory process. The ultrastructural integrity of the acinar cells was maintained after digestion and stimulation with secretagogues. Acini prepared from rats aged 24 - 48 hours responded to both CCK-8 and carbachol with significant increases in amylase release. Although typical biphasic dose response curves were obtained, the curves were shifted to the right by 1 - 2 log units, compared to the responses of adult acini. At ages younger than 24 hours, acini were insensitive to secretagogues but were sensitive to the calcium ionophore A23187. CCK receptors were virtually absent from membranes prepared from newborn pancreases, but binding of CCK, although small, was measurable at 12 hours and slowly increased up to 48 hours. A greater amount of binding was seen at 72 hours, which appeared constant up to 14 days. At 21 days, adult levels of binding were found. These results confirm previous studies that the rat pancreas is insensitive to secretagogues in the first 24 hours of life. After age 24 hours the secretory process is intact but less sensitive to secretory agents than the more mature pancreas. In the case of CCK, this may be due to lesser numbers of CCK receptors and/or affinity of CCK for its receptor.