Surgical treatment of infantile achalasia: a case report and literature review.

Allgrove syndrome is a rare genetic disorder typically manifested by alacrima, achalasia, and adrenal insufficiency, and is one of the rare causes of achalasia in infants. While the gold standard for achalasia treatment in adults is an esophageal myotomy with fundoplication, a standard treatment for infantile achalasia remains undetermined due to the low number of reported cases and rarity of the disease in this age group. We report a 7.7 kg infant with achalasia secondary to Allgrove syndrome who was successfully treated by Heller myotomy and simultaneous Toupet fundoplication. This case represents one of the smallest patients to ever be treated for achalasia and highlights the role that primary surgical therapy may have for the infantile variant of the disease.

A new animal model of postsurgical bowel inflammation and fibrosis: the effect of commensal microflora.

OBJECTIVE: Ileocaecal resection (ICR) is common in Crohn's disease. Inflammation and fibrosis frequently recur at the site of anastomosis or in the small intestine (SI). No animal models of postsurgical inflammation and fibrosis exist. A model of ICR was developed in interleukin 10 (IL10) null and wild-type (WT) mice to test the hypothesis that ICR promotes postsurgical inflammation and fibrosis in the SI or anastomosis of genetically susceptible IL10 null, but not WT or germ-free (GF)-IL10 null mice. METHODS: GF-IL10 null mice were conventionalised (CONV) and 3 weeks later randomised to ICR, transection (T) or no treatment (NoTx). Age-matched conventionally raised (CONV) WT and GF-IL10 null mice received ICR, T or NoTx. Animals were killed 28 days later. Histological scoring, real-time PCR for tumour necrosis factor alpha and collagen, and immunostaining for CD3(+) T cells assessed inflammation and fibrosis. RESULTS: After ICR, CONV-IL10 null, but not CONV-WT mice, developed significant inflammation and fibrosis in the SI and inflammation in anastomosis compared with NoTx or T controls. Fibrosis occurred in the anastomosis of both CONV-IL10 null and CONV-WT mice following ICR. GF-IL10 null mice developed little or no inflammation or fibrosis in the SI or anastomosis after ICR. CONCLUSIONS: ICR in CONV-IL10 null mice provides a new animal model of postsurgical inflammation and fibrosis in the SI and anastomosis. Absence of inflammation and fibrosis in the SI of CONV-WT and GF-IL10 null mice following ICR indicates that postsurgical small bowel disease occurs only in genetically susceptible IL10 null mice and is bacteria dependent.

Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor.

BACKGROUND: Epidermal growth factor (EGF) is likely involved during adaptation after small bowel resection (SBR) because some studies have shown enhanced adaptation by EGF administration. Because the major source of endogenous EGF in mice is the submandibular glands, we sought to determine the effect of submandibular gland excision (SAL) and luminal or systemic EGF replacement on adaptation after SBR. METHODS: A 50% proximal SBR or Sham-SBR (bowel transection and reanastomosis) was performed on male C57BL/6 mice after either SAL or gland mobilization only. Additional mice underwent both SBR and SAL and then received daily EGF or saline solution by intraperitoneal or orogastric administration. At 1 week, adaptation was characterized in the ileum as changes in villus height, DNA, and protein content. RESULTS: SAL significantly attenuated the increase in ileal villus height, total protein, and DNA content after SBR. Both systemic and oral EGF reversed these findings equally and significantly augmented all parameters of intestinal adaptation after SAL. CONCLUSIONS: Submandibular EGF is important for the adaptive response to massive SBR. As both luminal and systemic EGF equally reversed the findings following SAL and SBR, the specific site of action for endogenous EGF during adaptation is either the luminal or basolateral surface of the enterocyte.

Intestinal adaptation following massive small bowel resection in the mouse.

BACKGROUND: Transgenic mice represent powerful tools for studying the role of genes and their expression under multiple conditions, and they may provide a unique model for studies of intestinal adaptation after massive small bowel resection (SBR). This study characterized a successful model for SBR and intestinal adaptation in the mouse. STUDY DESIGN: Sham operation (bowel transection with reanastomosis) or SBR was performed on male C57BL/6 mice. A solid or liquid diet, various sizes of monofilament suture for the anastomosis, and resection of 50 or 75 percent of the proximal small intestine were studied. In other studies, intestinal adaptation was characterized as changes in intestinal wet weight, DNA, protein, villus height, crypt depth, and crypt cell proliferation rates at 12 hours, 24 hours, three days, and one, two, and four weeks after 50 percent SBR. RESULTS: Survival was significantly improved with a liquid diet (8 percent compared with 88 percent; p < .001) and modestly improved by using the smallest suture for anastomosis (60 percent for 7-0 compared with 88 percent for 9-0; p = not significant). Mice did not tolerate more than 50 percent SBR (16 percent survival rate for 75 percent SBR compared with 85 percent survival rate for 50 percent SBR; p < .01). Small bowel resection augmented ileal wet weight, DNA and protein content, villus height, crypt depth, and crypt-cell proliferation rates. CONCLUSIONS: Provision of a liquid diet, using a small suture for anastomosis, and resection of no more than 50 percent of the proximal small intestine are important for survival. This model will permit researchers using transgenic mice to better understand critical genes during intestinal adaptation after SBR.

Enterocyte apoptosis is increased following small bowel resection.

The intestinal mucosa is in a steady state of turnover as the rate of cellular proliferation is balanced by the rate of cell death. Although it is accepted that adaptation after small bowel resection (SBR) results in increased proliferation, its effect on apoptosis is not known. The purpose of this study was to determine the effect of adaptation following SBR on rates of enterocyte apoptosis. Male ICR mice underwent either 50% proximal SBR or sham operation (bowel transection/reanastomosis). After 12 and 24 hours, and 3 and 7 days, rates of proliferation were measured in the ileum as the percentage of crypt cells incorporating bromodeoxyuridine. Apoptosis was quantiated by end labeling of DNA strand breaks and propidium iodide staining of the number of apoptotic bodies per crypt and villus. Significant increases in enterocyte proliferation (30% to 40%) as well as apoptosis (57% to 87%) occurred at all time points following SBR when compared with sham-operated mice. Adaptation following SBR increases both the rate of enterocytc proliferation and the rate of apoptosis. Understanding the pathophysiology of intestinal adaptation and therapeutic interventions designed to augment this important response will require complete characterization of their effects on both proliferation and apoptosis.

Right lower quadrant pain in children caused by omental infarction.

BACKGROUND: Omental infarction is a rare cause of abdominal pain, with fewer than 300 cases reported in the literature. Only 15% of reported cases occur in the pediatric population. We present our experience with 18 children diagnosed with omental infarction admitted to Texas Children's Hospital over a 15-year period. STUDY DESIGN: A retrospective review of clinical records, diagnostic images, and pathologic findings was carried out for all children diagnosed with isolated omental infarction from 1986 to 2000 in order to analyze presenting signs and symptoms, preoperative imaging, surgical management, and postoperative outcomes. RESULTS: Eighteen children were treated for isolated omental infarction. There were 12 boys and 6 girls with an average age of 7.5 years (range 2 to 13). All patients presented with acute onset of right lower quadrant pain. Only 5 of 18 (24%) had associated gastrointestinal symptoms. The average temperature at presentation was 99.4 degrees F (+/- 0.78). The average white blood cell count was 11.4 (+/- 4.4). Fourteen patients had ultrasonographys performed preoperatively: 6 of 14 incorrectly diagnosed appendicitis, 4 of 14 were nondiagnostic and 4 of 14 correctly diagnosed omental infarction. Two of 18 patients underwent computed tomography scans, which were diagnostic for omental infarction. Resection of the infarcted omentum was performed in all patients and appendectomy in 16 of 18. Thirteen patients underwent an open procedure, 5 were performed laparoscopically. There were no postoperative complications. All patients had resolution of pain postoperatively and were discharged an average of 3.0 (+/- 0.9) days after admission. CONCLUSIONS: Omental infarction is an uncommon cause of right lower quadrant pain in children and is often diagnosed as appendicitis preoperatively. Ultrasonography and computed tomography can be diagnostic. Surgical resection of the infarcted omentum results in immediate resolution of pain with no morbidity.

Ovarian cysts in the pediatric population.

With the widespread availability and use of pelvic sonography, the rate at which ovarian cysts are detected in the pediatric population has increased, and such cysts are an important problem encountered in pediatric surgical practice. Rational management should take into account key factors such as symptoms, patient age, menarchal status, cysts size, and character, as well as associated medical conditions. The purpose of this review is to discuss the incidence and pathophysiology of ovarian cysts in children. A management strategy is presented based on the above-mentioned key factors.

Hypercalcemia associated with extracorporeal life support in neonates.

BACKGROUND/PURPOSE: Disturbances in calcium homeostasis are common at initiation of extracorporeal life support (ECLS). At the authors' institution many neonates undergoing ECLS have developed hypercalcemia. To determine the frequency of hypercalcemia in neonates during ECLS we performed retrospective chart review of neonates that required ECLS at our neonatal intensive care unit. METHODS: The authors identified 76 consecutive neonates who underwent ECLS before 10 days of age at Cincinnati Children's Hospital Medical Center from July 1, 1991 to June 30, 1996. The hospital charts and ELSO forms were reviewed. Demographic, clinical, and laboratory data for each of the patients were reviewed, both before initiation and during ECLS. Hypercalcemia was defined as total serum calcium concentration of greater than 11 mg/dL (2.74 mmol/L) on at least one occasion beyond the first 24 hours of ECLS. RESULTS: The hospital charts and ELSO forms from 70 patients were available for review. One patient was excluded because he was only on ECLS for 33 hours, and there were no calcium levels obtained after 24 hours of ECLS and until death. Twenty-five (36%) neonates undergoing ECLS had hypercalcemia (serum Ca > 11 mg/dL [2.74 mmol/L]). Hypercalcemia was associated with longer duration of ECLS (hypercalcemia group, 243 +/- 115 hours and normocalcemia group, 139 +/- 64 hours) and greater requirements for platelet transfusions (hypercalcemia group, 538 +/- 282 mL and normocalcemia group, 372 +/- 233 mL). This could not be explained by differences in primary diagnosis, amounts of calcium administered, and acid-base status. CONCLUSIONS: Hypercalcemia was found to be common in neonates that require ECLS and is associated with longer duration of ECLS support. Conservative calcium administration for neonates while on ECLS may be warranted.

Epidermal growth factor upregulates the expression of its own intestinal receptor after small bowel resection.

BACKGROUND/PURPOSE: Epidermal growth factor (EGF) binds to its enterocyte receptor and enhances intestinal adaptation after massive small bowel resection (SBR). To ascertain the mechanism for enhanced adaptation by EGF, we sought to determine the effect of EGF administration on in vivo expression of the intestinal EGF receptor after SBR. METHODS: Male ICR mice underwent a 50% proximal SBR and then were assigned randomly to EGF (150 microg/kg/d) or saline by twice daily intraperitoneal injection. After 3 days, the ileum was harvested and total protein and DNA content were measured. Northern hybridization and a ribonuclease protection assay were used to detect qualitative and quantitative expression of EGF receptor mRNA. The remaining ileum was pooled for each group and Western blotting used to determine expression of EGF receptor protein. RESULTS: EGF augmented adaptation after SBR as monitored by significant increases in ileal protein (2.7+/-0.08 saline versus 3.9+/-0.17 mg/cm EGF; P<.001) and DNA (55.8+/-1.6 saline versus 104+/-8.4 microg/cm EGF; P<.001) content. Northern blotting results showed a marked (>fivefold) increase in ileal EGF receptor mRNA, which was confirmed with the ribonuclease protection assay. Administration of EGF after SBR induced a similar expression of EGF receptor protein. CONCLUSIONS: EGF enhanced intestinal adaptation after SBR. This augmented response is associated with increased ileal expression of EGF receptor mRNA and protein. Increased EGF receptor expression and subsequent enhanced ligand/ receptor activity may be one important mechanism for the beneficial effect of EGF administration during intestinal adaptation.

Intestinal adaptation is enhanced by epidermal growth factor independent of increased ileal epidermal growth factor receptor expression.

BACKGROUND/PURPOSE: Intestinal adaptation after massive small bowel resection (SBR) is augmented by epidermal growth factor (EGF) via an unknown mechanism. We recently have observed that EGF increases the expression of EGF receptor mRNA and protein content in the remnant ileum after SBR. The purpose of this study was to determine whether the magnitude of EGF-induced receptor expression correlates with intestinal adaptation. METHODS: A 50% proximal SBR or sham operation (bowel transection with reanastomosis) was performed on male ICR mice. Animals from each group were then selected randomly to receive either human recombinant EGF (150 microg/kg/d) or saline by twice daily intraperitoneal injections. The remnant ileum was harvested at 1 week, and parameters of adaptation measured as changes in protein content. Ileal EGF receptor mRNA was quantitated using a ribonuclease protection assay. Changes in the expression ileal EGF receptor protein were determined by Western blot after immunoprecipitation. Comparisons of mean values between groups was performed using analysis of variance (ANOVA) and a P value of less than .05 was considered significant. Values are presented as mean +/- SEM. RESULTS: EGF was mitogenic to the ileum after sham operation as monitored by increases in ileal protein content (2.21 +/- 0.002 mg/cm Sham v 2.97 +/- 0.25 mg/cm Sham +/- EGF; P < .05). After SBR, adaptation resulted in increased ileal protein content (4.45 +/- 0.27 mg/cm), which was substantially boosted by EGF (5.98 +/- 0.39 mg/cm; P < .05). No differences were detected in ileal EGF receptor mRNA or protein expression between Sham or SBR groups that did not receive EGF. However, EGF significantly enhanced the expression of ileal EGF receptor mRNA to an equal extent after both sham and SBR (approximately threefold). The magnitude of this increase in EGF receptor protein (four- to sixfold) was similar in both EGF groups as shown by Western blotting. CONCLUSIONS: Changes in ileal EGF receptor expression are not mandatory for adaptation to occur. EGF upregulates the expression of mRNA and protein for its own intestinal receptor in vivo. Because EGF-induced receptor expression was comparable after both SBR and Sham operation, the beneficial effect of EGF during adaptation is likely caused by other factors in addition to increased receptor expression.

A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation.

While the pathophysiology of intestinal adaptation following small bowel resection (SBR) is not well understood, there is evidence to suggest an important role for epidermal growth factor (EGF) in this process. In waved-2 mice, a naturally occurring mutation results in reduced EGF receptor protein tyrosine kinase activity. We tested the hypothesis that an intact EGF receptor is essential for adaptation by subjecting this strain of mice to SBR. A 50% proximal SBR or sham operation (bowel transection with reanastomosis only) was performed in waved-2, heterozygous, and wildtype mice. After 3 days, adaptation was characterized in the remnant ileum as changes in DNA and protein content per unit length. Villus height and crypt depth were measured, and crypt cell proliferation rates were determined by the percentage of crypt cells taking up 5-bromodeoxyuridine. Following sham surgery, all mice regained their preoperative weight by the third postoperative day. After SBR, all mice gained weight while the waved-2 mice did not. Ileal DNA and protein significantly increased after SBR in wild-type and heterozygous mice while these parameters were unchanged in the waved-2 mice. Villus height and crypt cell proliferation increased in response to SBR in all groups; however, the changes were less pronounced in the waved-2 mice. Adaptation after SBR is impaired in waved-2 mice. Signal transduction by the EGF receptor is a critical component of this response. These data endorse a crucial role for EGF and its receptor in the pathogenesis of intestinal adaptation.

The EGF\EGF-receptor axis modulates enterocyte apoptosis during intestinal adaptation.

BACKGROUND: Adaptation after small bowel resection (SBR) is characterized by a new set point in the balance of enterocyte proliferation and apoptosis. Since epidermal growth factor (EGF) augments both proliferation and adaptation, we sought to determine the effect of EGF receptor manipulation on apoptosis following SBR. MATERIALS AND METHODS: Male ICR mice underwent 50% SBR or sham operation (bowel transection with reanastomosis) and then were given EGF (50 microg/kg/day) or saline by orogastric gavage. At 1 week, a proliferation index (PI) was measured in the ileum by BrdU uptake and an apoptosis index in crypts (cAI) and villi (vAI) scored by counting apoptotic bodies in enterocytes. In other experiments, AI was scored after SBR in mice with defective receptors (waved-2). Results are expressed as means +/- SE and evaluated statistically using ANOVA. # denotes P < 0.001. RESULTS: Following SBR, EGF increased PI (40 +/- 2% vs 50 +/- 1% BrdU + cells; #), villus height (252 +/- 4 micro(m) vs 401 +/- 15 micro(m); #), and crypt depth (77.3 +/- 1.5 micro(m) vs 120.8 +/- 5 micro(m); #). When compared with sham, SBR resulted in increased cAI (0.3 +/- 0.02 vs 2.0 +/- 0.1; #) and vAI (0.4 +/- 0.05 vs 1.1 +/- 0.1; #). EGF attenuated both cAI (0.5 +/- 0. 04) and vAI (0.5 +/- 0.03) following SBR. In the waved-2 mice, the highest levels of cAI (3.1 +/- 0.2) and vAI (3.6 +/- 0.3) were noted after SBR. CONCLUSIONS: Enterocyte apoptosis during adaptation is attenuated by EGF and exaggerated when the EGF receptor is defective. In addition to enhancing proliferation, suppression of apoptosis may provide a previously unrecognized mechanism for the beneficial effect of EGF during intestinal adaptation.

Epidermal growth factor receptor expression following small bowel resection.

BACKGROUND: Adaptation following massive small bowel resection (SBR) is an important compensatory response. While epidermal growth factor (EGF) has been shown to augment this response, the mechanism and role of EGF and its intestinal receptor (EGF-R) during adaptation are not known. The purpose of this study was to determine the effect of massive SBR and adaptation on intestinal expression of EGF-R. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent either a 75% mid-SBR with primary reanastomosis or sham operation (bowel transection with reanastomosis). Ileal mucosa was harvested from animals of each group at 6 and 12 hr, 1, 3, and 5 days, and 1, 2, and 4 weeks after operation. Expression of EGF-R protein was studied by Western blotting. Expression of EGF-R mRNA was determined by quantitative reverse-transcriptase polymerase chain reactions normalized to beta-actin. RESULTS: When compared with sham, SBR resulted in a modest (32%) increase in the expression of EGF-R mRNA at 1 week (P < 0.003). A twofold greater expression of EGF-R protein corresponded to this time point. While not statistically significant, expression of EGF-R mRNA was slightly greater after SBR at every other time point measured. CONCLUSION: Following massive SBR, expression of both EGF-R mRNA and protein is slightly increased in the ileum with a more pronounced increase in protein. These findings, which have not previously been reported, suggest that changes in EGF-R signaling may not play a major role during the initiation and or progression of intestinal adaptation following massive SBR.

Intestinal overexpression of EGF in transgenic mice enhances adaptation after small bowel resection.

The effect of direct intestinal overexpression of epidermal growth factor (EGF) on postresection adaptation has been investigated by the production of transgenic mouse lines. A murine pro-EGF cDNA construct was produced, and expression of the EGF construct was targeted to the small intestine with the use of the rat intestinal fatty acid-binding protein promoter. An approximately twofold increase in intestinal EGF mRNA and protein was detected in heterozygous mice. No changes in serum EGF levels were noted. Except for a slightly shortened small intestine, no other abnormal phenotype was observed. Intestinal adaptation (increases in body weight, DNA, protein content, villus height, and crypt depth) was markedly enhanced after a 50% proximal small bowel resection in transgenic mice compared with nontransgenic littermates. This transgenic mouse model permits the study of intestinal adaptation and other effects of EGF in the small intestine in a more physiological and directed manner than has been previously possible. These results endorse a direct autocrine/paracrine mechanism for EGF on enterocytes as a means to enhance adaptation.

Epidermal growth factor augments adaptation following small bowel resection: optimal dosage, route, and timing of administration.

BACKGROUND: In assorted animal models of small bowel resection (SBR), exogenous epidermal growth factor (EGF) has been shown to augment intestinal adaptation. This study was designed to elucidate the optimal dose, route, and timing of exogenous EGF to boost adaptation in our murine model of SBR. METHODS: Male ICR mice underwent either 50% proximal SBR or sham surgery (bowel transection with reanastomosis) and then randomized to receive either saline or human recombinant EGF (5, 50, 150, or 300 microg/kg/day) by twice daily intraperitoneal (i.p.) injection or orogastric gavage (o.g.). At 7 days, protein and DNA content, crypt depth, and villus height were determined in the ileum. The premium dose and route was then given for 1 week either during (1 week after SBR) or after the adaptive phase (1 month after SBR). Differences between group means were analyzed using ANOVA. A P < 0.05 was considered significant. RESULTS: EGF enhanced DNA and protein content, crypt depth, and villus height to the greatest extent at a dosage of 50 microg/kg/day by the o.g. route. EGF had no significant effect on enhancing adaptation when given after the adaptive response had already occurred. CONCLUSIONS: Intestinal adaptation is optimally enhanced by a specific dose and route of EGF. Exogenous EGF enhances adaptation only during the adaptive response to SBR and not after it has already taken place. Determination of the best circumstances for EGF administration will permit a systematic approach toward understanding a mechanism for the beneficial effect of EGF during intestinal adaptation.