Image based feasibility of renal sparing surgery for very low risk unilateral Wilms tumors: a report from the Children's Oncology Group.

PURPOSE: Nephrectomy with lymph node sampling is the recommended treatment for children with unilateral Wilms tumor under the Children's Oncology Group protocols. Using radiological assessment, we determined the feasibility of performing partial nephrectomy in a select group of patients with very low risk unilateral Wilms tumor. MATERIALS AND METHODS: We reviewed imaging studies of 60 patients with a mean age of less than 2 years with very low risk unilateral Wilms tumor (mean weight less than 550 gm) to assess the feasibility of partial nephrectomy. We evaluated percentage of salvageable parenchyma, tumor location and anatomical features preventing a nephron sparing approach. RESULTS: A linear relationship exists between tumor weight and computerized tomography estimated tumor volume. Mean tumor weight in the study population was 315 gm. Partial nephrectomy was deemed feasible in only 5 of 60 patients (8%). CONCLUSIONS: When considering a select population with very low risk unilateral Wilms tumor (lower volume tumor), only a small percentage of nonpretreated patients are candidates for nephron sparing surgery.

Non-operative treatment versus percutaneous drainage of pancreatic pseudocysts in children.

PURPOSE: The objective of this study was to characterize the clinical course and outcomes of children with pancreatic pseudocysts that were initially treated non-operatively or with percutaneous drainage. METHODS: A retrospective review of children with pancreatic pseudocysts over a 12-year period was completed. Categorical variables were compared using Fischer's exact method and the Student's t test was used to compare continuous variables. Analysis was done using logistic and linear regression models. RESULTS: Thirty-six children met the criteria for pancreatic pseudocyst and 33 children were treated either non-operatively or with percutaneous drainage. Of the 22 children managed non-operatively, 17 required no additional intervention (77 %) and five required surgery. Operative procedures were: Frey procedure (3), distal pancreatectomy (1), and cystgastrostomy (1). Eight of the 11 children treated with initial percutaneous drainage required no additional treatment (72 %). The other three children underwent distal pancreatectomy. Success of non-operative management or percutaneous drainage was not dependent on size or complexity of the pseudocyst Logistic regression did not identify any patient demographic (gender, age, and weight), etiologic (trauma, non-traumatic pancreatitis) or pseudocyst characteristic (size, septations) that predicted failure of non-operative therapy. CONCLUSIONS: In children, pancreatic pseudocysts can frequently be managed without surgery regardless of size or complexity of the pseudocyst. When an intervention is needed, percutaneous drainage can be performed successfully, avoiding the need for major surgical intervention in the majority of patients.

Laparoscopic appendectomy for perforated appendicitis: a comparison with open appendectomy.

BACKGROUND: The role of laparoscopic appendectomy for perforated appendicitis remains controversial. This study aimed to compare laparoscopic and open appendectomy outcomes for children with perforated appendicitis. METHODS: Over a 36-month period, 111 children with perforated appendicitis were analyzed in a retrospective review. These children were treated with either laparoscopic (n = 59) or open appendectomy. The primary outcome measures were operative time, length of hospital stay, time to adequate oral intake, wound infection, intraabdominal abscess formation, and bowel obstruction. RESULTS: The demographic data, presenting symptoms, preoperative laboratory values, and operative times (laparoscopic group, 61 +/- 3 min; open group, 57 +/- 3 were similar for the two groups (p = 0.3). The time to adequate oral intake was 104 +/- 7 h for the laparoscopic group and 127 +/- 12 h for the open group (p = 0.08). The hospitalization time was 189 +/- 14 h for the laparoscopic group, as compared with 210 +/- 15 h for the open group (p = 0.3). The wound infection rate was 6.8% for the laparoscopic group and 23% for the open group (p < 0.05). The wounds of another 29% of the patients were left open at the time of surgery. The postoperative intraabdominal abscess formation rate was 13.6% for the laparoscopic group and 15.4% for the open group. One patient in each group experienced bowel obstruction. CONCLUSIONS: Laparoscopic appendectomy for the children with perforated appendicitis in this study was associated with a significant decrease in the rate of wound infection. Furthermore, on the average, the children who underwent laparoscopic appendectomy tolerated enteral feedings and were discharged from the hospital approximately 24 h earlier than those who had open appendectomy.

Comparison of the incidence of complications in open and laparoscopic pyloromyotomy: a concurrent single institution series.

PURPOSE: The purpose of this study was to compare the incidence and type of technical complications seen in a concurrent series of pyloromyotomies done open and laparoscopically. METHODS: The medical records of all patients who underwent pyloromyotomy for congenital hypertrophic pyloric stenosis over a 66-month period were reviewed (n = 457). Information obtained included age, sex, weight, operating time, and intraoperative and postoperative complications. RESULTS: Four hundred fifty-seven pyloromyotomies were equivalently divided between the 2 techniques (232 laparoscopic, 225 open). Demographic characteristics and operating times were similar. There were no deaths in the series. The overall incidences of complications were similar in the 2 groups (open, 4.4%; laparoscopic, 5.6%). There was a greater rate of perforation with the open technique and a higher rate of postoperative problems including incomplete pyloromyotomy in the laparoscopic group. CONCLUSIONS: The open and laparoscopic approaches have similar overall complication rates. The distribution and the type of complications differ, however.

ANG II type 1 receptor downregulation does not require receptor endocytosis or G protein coupling.

ANG II type 1 (AT(1)) receptors respond to sustained exposure to ANG II by undergoing downregulation of absolute receptor numbers. It has been assumed previously that downregulation involves endocytosis. The present study hypothesized that AT(1) receptor downregulation occurs independently of receptor endocytosis or G protein coupling. Mutant AT(1) receptors with carboxy-terminal deletions internalized <5% of radioligand compared with 65% for wild-type AT(1) receptors. The truncated AT(1) receptors retained the ability to undergo downregulation. These data suggest the existence of an alternative pathway to AT(1) receptor degradation that does not require endocytosis, per se. Point mutations in either the second transmembrane region or second intracellular loop impaired G protein (G(q)) coupling. These receptors exhibited a biphasic pattern of downregulation. The earliest phase of downregulation (0-2 h) was independent of coupling to G(q), but no additional downregulation was observed after 2 h of ANG II exposure in the receptors with impaired coupling to G(q). These data suggest that coupling to G(q) is required for the later phase (2-24 h) of AT(1) receptor downregulation.

Cholinergic intrapancreatic neurons induce Ca²+ signaling and early-response gene expression in pancreatic acinar cells.

Pancreatic exocrine function has been demonstrated to be under neuronal regulation. The pathways responsible for this effect, and the long-term consequences of such interactions, are incompletely described. The effects of neuronal depolarization on pancreatic acinar cells were studied to determine whether calcium signaling and c-fos expression were activated. In pancreatic lobules, which contain both neurons and acinar cells, agonists that selectively stimulated neurons increased intracellular calcium in acinar cells. Depolarization also led to the expression of c-fos protein in 24% +/- 4% of the acinar cells. In AR42J pancreatic acinar cells, cholinergic stimulation demonstrated an average increase of 398 +/- 19 nmol/L in intracellular calcium levels, and induced c-fos expression that was time and dose dependent. The data indicate that intrapancreatic neurons induce Ca²+ signaling and early-response gene expression in pancreatic acinar cells.

Calcium signaling induced by angiotensin II in the pancreatic acinar cell line AR42J.

The purpose of this study was to characterize the nature and mechanisms of angiotensin II-evoked calcium signaling in AR42J cells. Cytosolic calcium concentrations were determined using fura-2-based microfluorimetry. Angiotensin II causes elevations in free cytosolic calcium ([Ca2+]i) in the rat pancreatic acinar cell line AR42J. The mechanisms of angiotensin II-evoked calcium signaling were examined using fura-2-based fluorescent digital microscopy. Angiotensin II caused dose-dependent increments in [Ca2+]i over a concentration range of 0.1-1,000 nM, with an average increment of 243 +/- 16 nM at an angiotensin II concentration of 1,000 nM. Dup753, an AT1-specific antagonist, inhibited angiotensin II-evoked signaling, whereas the AT2 antagonist PD123,319 had no effect. Preincubation with the phospholipase C inhibitor U73122 reduced the response in [Ca2+]i to 25% of that of the control. Thapsigargin abolished angiotensin II-evoked calcium signaling. The inositol 1,4,5-trisphosphate receptor antagonist heparin introduced by radiofrequency electroporation inhibited responses to 46 +/- 6% of controls. Angiotensin II-evoked signals were reduced in magnitude and duration by elimination of Ca2+ from the extracellular buffer. Preincubation with pertussis toxin (100 ng/ml) had no effect. Angiotensin II did not stimulate cyclic AMP or suppress vasoactive intestinal peptide stimulated cyclic AMP production over the concentration range that caused Ca2+ signaling.

Capacitative Ca2+ entry in enteric glia induced by thapsigargin and extracellular ATP.

Mobilization of intracellular Ca2+ stores is coupled to Ca2+ influx across the plasma membrane, a process termed capacitative Ca2+ entry. Capacitative Ca2+ entry was examined in cultured guinea pig enteric glia exposed to 100 microM ATP, an inositol trisphosphate-mediated Ca2+-mobilizing agonist, and to 1 microM thapsigargin, an inhibitor of microsomal Ca2+ ATPase. Both agents caused mobilization of intracellular Ca2+ stores followed by influx of extracellular Ca2+. This capacitative Ca2+ influx was inhibited by Ni2+ (88 +/- 1%) and by La3+ (87 +/- 1%) but was not affected by L- or N-type Ca2+ channel blockers. Pretreatment of glia with 100 nM phorbol 12-myristate 13-acetate for 24 h decreased capacitative Ca2+ entry by 48 +/- 2%. Chelerythrine (0.1-10 microM), a specific antagonist of protein kinase C (PKC), dose dependently inhibited capacitative Ca2+ entry. The nitric oxide synthase inhibitor NG-nitro-L-arginine (1 mM) decreased Ca2+ influx by 42 +/- 1%. Capacitative Ca2+ entry was inhibited to a similar degree by the guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Capacitative Ca2+ entry occurs in enteric glial cells via lanthanum-inhibitable channels through a process regulated by PKC and nitric oxide.

Endothelin-stimulated capacitative calcium entry in enteric glial cells: synergistic effects of protein kinase C activity and nitric oxide.

Depletion of intracellular calcium stores by agonist stimulation is coupled to calcium influx across the plasma membrane, a process termed capacitative calcium entry. Capacitative calcium entry was examined in cultured guinea pig enteric glial cells exposed to endothelin 3. Endothelin 3 (10 nM) caused mobilization of intracellular calcium stores followed by influx of extracellular calcium. This capacitative calcium influx was inhibited by Ni2+ (89 +/- 2%) and by La3+ (78 +/- 2%) but was not affected by L-, N-, or P-type calcium channel blockers. Chelerythrine, a specific antagonist of protein kinase C, dose-dependently inhibited capacitative calcium entry. The nitric oxide synthase inhibitor NG-nitro-L-arginine decreased calcium influx in a dose-dependent manner. The combination of chelerythrine and NG-nitro-L-arginine produced synergistic inhibitory effects. Capacitative calcium entry occurs in enteric glial cells via lanthanum-inhibitable channels through a process regulated by protein kinase C and nitric oxide.

Immediate and long-term results of surgical management of low imperforate anus in girls.

BACKGROUND: The majority of girls with imperforate anus are reported to have a malformation of the low variety. Despite this, much of the literature has focused on the more complex, high lesions. METHODS: This study reviews our experience with 44 girls with low imperforate anus from a 22-year period. RESULTS: The incidence of associated anomalies was 61%, which is higher than generally reported. All patients in the study had anal fistulae. Fifty-seven percent had perineal fistulae, 23% had fourchette fistulae, and 20% had vestibular fistulae. Cutback anoplasty was performed in 55%, Potts transfer anoplasty was used in 27%, and 18% of patients were treated with either limited posterior sagittal anorectoplasty or anterior sagittal anorectoplasty. Surgical complications were uncommon. Long-term follow-up was carried out by telephone survey. This showed 89% of the girls to be successfully toilet trained. However, 47% of patients experience at least occasional soilage or episodic fecal incontinence. CONCLUSIONS: Low imperforate anus can be successfully treated using a variety of procedures without colostomy. Most girls with low imperforate anus are successfully toilet trained, but problems with continence persist in a significant number of these patients.

Tachykinin neuropeptide-evoked intracellular calcium transients in cultured guinea pig myenteric neurons.

Substance P and related tachykinins are present in the mammalian gut and act as neurotransmitters. Microfluorimetric measurement of intracellular calcium ([Ca2+]i) was used to study tachykinin-sensitive myenteric neurons. Substance P (0.001-10 microM) evoked concentration-dependent increases in percentage of neurons responding (6-75%) and delta [Ca2+]i (88 +/- 24 to 212 +/- 16 nM). Neurokinin A (0.001-1 microM) produced similar responses. Removal of extracellular Ca2+ abolished substance P-induced Ca2+ signals, as did the addition of the Ca2+ channel blockers lanthanum chloride (5 mM) and nickel chloride (2.5 mM). Both nifedipine (1-50 microM) and diltiazem (1-50 microM) inhibited substance P-evoked Ca2+ responses in a dose-dependent manner. Substance P and related tachykinins evoke Ca2+ signaling in cultured myenteric neurons by the influx of extracellular Ca2+ through L and N-type plasma membrane Ca2+ channels.

PACAP-38 causes phospholipase C-dependent calcium signaling in rat acinar cell line.

BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP-38), a neuropeptide of the vasoactive intestinal peptide/secretin family, localizes to intrapancreatic neurons and stimulates exocrine secretion from the pancreas. PACAP-38 stimulates calcium signaling in the rat pancreatic cell line AR42J. The purpose of this study was to elucidate the mechanisms of PACAP-evoked calcium signaling in these cells. METHODS: Continuous measurements of intracellular calcium were taken by fluorescent digital microscopy with the dye fura-2. Mechanisms of PACAP-38-evoked calcium signals were determined by a panel of inhibitors. Inositol phosphates production in response to PACAP-38 was measured. The ability of PACAP-38 to stimulate amylase release was used to determine a relevant dose range for these studies. RESULTS: We have shown that (1) AR42J cells respond to PACAP-38 with biphasic increases in [Ca2+]i in a dose-dependent fashion; (2) PACAP-38 acts through phospholipase C to release inositol triphosphate (IP3)-sensitive Ca2+ stores with (3) a subsequent influx of extracellular Ca2+. CONCLUSIONS: PACAP-38 activates calcium signaling through phospholipase C at concentrations that stimulate amylase release in AR42J cells.

Conservative management of mesenchymal hamartoma of the liver.

The natural history of mesenchymal hamartoma of the liver is poorly understood. This case demonstrates the course of a biopsy-proven mesenchymal hamartoma using sequential computed tomography (CT) examinations. These CT scans show initial expansion of the lesion with subsequent involution. The spontaneous resolution in this patient suggests the possibility of conservative management of asymptomatic mesenchymal hamartomas. The case is presented, and the literature on mesenchymal hamartoma is reviewed.

Meal-stimulated canine jejunal ionic absorption. Influence of mucosal neural blockade.

The oral ingestion of a meal or the delivery of nutrients directly to the stomach or duodenum stimulates water and ion absorption from the proximal jejunal lumen. To further investigate this phenomenon, this study tested two hypotheses: (1) direct jejunal nutrient delivery stimulates jejunal absorption, and (2) the signal for jejunal absorption requires intact enteric neurotransmission and will therefore be altered by mucosal neural blockade with the local anesthetic bupivacaine. Intestinal absorption studies (N = 52) were performed on eight dogs with 25-cm jejunal Thiry-Vella fistulas (TVF) and feeding jejunostomies. Luminal perfusion with [14C]PEG was used to calculate TVF absorption of H2O, Na+, and Cl-. Six groups were randomly studied over 4 hr. Each group incorporated a basal hour, a TVF or jejunostomy treatment hour, and an oral (groups 1 and 3) or a jejunal (groups 4 and 6) meal stimulus. The oral and jejunal meals were isocaloric and of identical composition. Groups 1-3 had saline (as a control) or 0.75% bupivacaine applied to the lumen of the TVF. Groups 5 and 6 had 0.75% bupivacaine application to the feeding jejunostomy. Both the oral and the jejunal meal stimuli resulted in a significant proabsorptive response in the TVF. TVF bupivacaine reduced basal absorption but did not diminish the meal-induced proabsorptive response. Treatment of the jejunostomy with bupivacaine caused no change in basal or postmeal absorption in the TVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic utility of lower extremity radiographs of young children with gait disturbance.

The diagnostic utility of lower extremity radiographs was evaluated using 84 outpatients 1 to 5 years of age with gait disturbance whose lower extremities appeared physically normal. Chief complaints included limp (65 children [77%]), refusal to walk or stand (37 children [44%]), and frequent falling (6 children [7%]). A total of 43 children (51%) had more than one complaint. The mean age of patients was 26 months and the median duration of symptoms was 1 day. Trauma was reported in 43 (51%) cases and fever in 14 (17%). Results of radiographical studies appeared normal in 81 children (96%), demonstrated soft tissue swelling in 2 children, and revealed a bony island in 1 child. In 1 patient admitted to the hospital for failure to thrive and irritability, and whose radiographic results appeared normal, findings consistent with osteomyelitis later developed. Of the remaining children, 68 (81%) were available for follow-up observation 4 to 28 months after the initial visit and all reported spontaneous resolution of the initial complaint. It was concluded that in a well-appearing child with an otherwise normal physical examination results, an acute gait disturbance is likely to be a self-limiting condition and radiographs are unlikely to contribute to the diagnosis.

Dose-responsive characteristics of meperidine sedation in preschool children.

Using double-blind conditions, 60 uncooperative and fearful preschool children (24-66 months) received intramuscular injections of meperidine 0.25, 0.50, 1.00 mg/lb or placebo prior to restorative dental treatment. Behavior was assessed by the dentist and an independent observer during five specific treatment procedures. Behavioral ratings found meperidine to be an effective sedative, with 0.50 mg/lb and 1.00 mg/lb being significantly more effective than placebo (P less than 0.05, Kruskal-Wallis). Children receiving 1.0 mg/lb of meperidine had significantly more nausea and vomiting than patients receiving lower doses of the drug (P less than 0.05, Chisquare). Physiologic monitoring demonstrated that the highest dose of meperidine was associated with transient drops in arterial oxygen saturation. Meperidine sedation was found to be more effective for older children (37-66 months) and for children initially rated as being only moderately uncooperative and fearful.