Intracellular copper accumulation enhances the growth of Kineococcus radiotolerans during chronic irradiation.

The actinobacterium Kineococcus radiotolerans is highly resistant to ionizing radiation, desiccation, and oxidative stress, though the underlying biochemical mechanisms are unknown. The purpose of this study was to explore a possible linkage between the uptake of transition metals and extreme resistance to ionizing radiation and oxidative stress. The effects of six different divalent cationic metals on growth were examined in the absence of ionizing radiation. None of the metals tested were stimulatory, though cobalt was inhibitory to growth. In contrast, copper supplementation dramatically increased colony formation during chronic irradiation. K. radiotolerans exhibited specific uptake and intracellular accumulation of copper, compared to only a weak response to both iron and manganese supplementation. Copper accumulation sensitized cells to hydrogen peroxide. Acute-irradiation-induced DNA damage levels were similar in the copper-loaded culture and the age-synchronized no-copper control culture, though low-molecular-weight DNA was more persistent during postirradiation recovery in the Cu-loaded culture. Still, the estimated times for genome restoration differed by only 2 h between treatments. While we cannot discount the possibility that copper fulfills an unexpectedly important biochemical role in a low-radioactivity environment, K. radiotolerans has a high capacity for intracellular copper sequestration and presumably efficiently coordinated oxidative stress defenses and detoxification systems, which confers cross-protection from the damaging effects of ionizing radiation.

Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis.

OBJECTIVES: To evaluate the relationship between the severity of necrotizing enterocolitis (NEC) and circulating concentrations of proinflammatory cytokines interleukin (IL)-1beta and IL-8 and counterinflammatory cytokines IL-1 receptor antagonist (IL-1ra) and IL-10. These cytokines have been associated with bowel injury or inflammation and may be released more slowly or later than previously examined cytokines. Also, to determine if any one of these cytokines will predict the eventual severity of NEC when measured at symptom onset. METHOD: Serial blood samples at onset, 8, 24, 48, and 72 hours were obtained from newborn infants with predefined signs and symptoms of NEC. Normal levels were defined from weight-, gestation-, and age-matched controls. Concentrations of the four cytokines were determined by enzyme-linked immunosorbent assay and compared throughout the time period by stage of NEC, using sepsis as a co-factor. Mean concentrations of each cytokine at onset were compared with the controls. Threshold values were obtained with the best combination of high sensitivity and high specificity for defining stage 1 NEC or for diagnosing stage 3 NEC at onset. RESULTS: There were 12 cases of stage 1, 18 cases of stage 2, and 6 cases of stage 3 NEC included in the study, as well as 20 control infants. Concentrations of IL-8 and IL-10 were significantly higher in infants with stage 3 NEC from onset through 24 hours compared with infants with less severe NEC. At onset, concentrations of all four cytokines were significantly higher in stage 3 NEC. To identify, at onset, the infants with a final diagnosis of stage 3 NEC, an IL-1ra concentration of >130 000 pg/mL had a sensitivity of 100% and a specificity of 92%. At 8 hours, an IL-10 concentration of >250 pg/mL had a sensitivity of 100% and a specificity of 90% in identifying stage 3 NEC in infants with symptoms suggestive of NEC at onset. CONCLUSIONS: The severity of NEC and its systemic signs and symptoms are not due to a deficiency of counterregulatory cytokines. In fact, mean concentrations of IL-1ra in NEC are higher than what has been reported in other populations. The cytokines IL-8, IL-1ra, and IL-10 are released later or more slowly after a stimulus and may be more useful in identifying, within hours of symptom onset, which infant will develop significant NEC.

Unilateral pulmonary agenesis, esophageal atresia, and distal tracheoesophageal fistula.

A small-for-gestational-age, premature infant with the combination of unilateral pulmonary agenesis, esophageal atresia, and distal tracheoesophageal fistula was treated successfully by early gastrostomy and delayed fistula division with esophagoesophagostomy. Only 2 other successfully treated cases have been reported previously. Both were full-term infants treated with early division of the tracheoesophageal fistula and esophagoesophagostomy. Gestational age, size, and associated medical problems need to be considered when planning operative therapy for these babies.

Physiological Diversity of Rhizoplane Diazotrophs of the Saltmeadow Cordgrass, Spartina patens: Implications for Host Specific Ecotypes.

Diazotrophic bacteria are important contributors to salt marsh productivity, but the biotic and abiotic factors that influence their distributions and function and the extent of their diversity cannot be understood in the absence of physiological information. Here we examine the physiological diversity and distribution patterns of diazotrophic bacteria associated with the rhizoplane of the saltmeadow cordgrass, Spartina patens, in comparison with diazotrophs from other intertidal grasses (tall and short form Spartina alterniflora and Juncus roemerianus) from the same salt marsh. S. patens plants were collected from two distinct habitats, and a total of 115 strains (111 Gram negative and 4 Gram positive strains) were isolated into pure culture by stab inoculating roots and rhizomes into combined nitrogen-free semisolid media. Most strains were microaerophilic and approximately one-half were motile. API test strips were used to eliminate redundancy within the culture collection, resulting in 21 physiologically different API groups (17 Gram negative and 4 Gram positive groups). A representative strain from each API group was selected for dot blot hybridization with a nifH specific probe and 16 strains (13 Gram negative and 3 Gram positive) were scored as positive. The nifH positive API group representative strains were characterized further using BIOLOG test plates. Substrate utilization potentials defined two S. patens strain clusters, and only one S. patens strain was physiologically similar to any other strain from a different host plant origin. No distinctions could be made based on the different S. patens habitats, suggesting that the host plant may have a greater impact than abiotic environmental conditions on the distributions of the rhizoplane diazotrophs recovered.

Spirometric and endoscopic evaluation of airway collapse in infants with bronchopulmonary dysplasia.

We evaluated eight infants with bronchopulmonary dysplasia (BPD) at ages from 2 to 13 months who had repeated episodes of clinical respiratory deterioration associated with agitation. These episodes limited further weaning from ventilation or necessitated recurrent intubation and reinstitution of ventilation. All infants underwent spirometric evaluation and six also had endoscopic examination during simulated agitation episodes (elicited by toe pinching). All babies were found to have a very prolonged near zero expiratory airflow pattern, accompanied by vigorous diaphragmatic and abdominal muscle activity and rapid development of hypoxia. Six patients had endoscopically documented tracheal collapse under the same simulated circumstances. The episodes ceased with calming or sedation of the infants.

Blunt abdominal trauma: exploratory laparotomy or peritoneal lavage?

In contrast to other series purporting advantages of routine lavage [20], our data support the position that, in patients with blunt abdominal trauma, certain criteria eliminate the need for peritoneal lavage and make this procedure an unwise investment of valuable time on a routine basis. Criteria such as evidence of hollow organ rupture on radiologic studies, gross abdominal wall defects (excluding simple lacerations), rapidly increasing abdominal distention, uncorrectable hypotension and isolated rigidity on abdominal examination in an otherwise intact and cooperative patient, should be considered indications for laparotomy. In a stable patient with associated injuries or altered central nervous system status, abdominal examination should be viewed as suspect and peritoneal lavage considered mandatory. However, in over one fourth of cases, positive lavage may fail to correlate with intraabdominal injury of a degree that necessitates operative repair. In patients admitted for observation of abdominal injuries with concurrent alterations in central nervous system status or associated injuries that hinder accurate abdominal examination when no urgency exists, we support the opinion that selective use of peritoneal lavage will save unnecessary delay in diagnosis and operative treatment. The highly lethal nature of multiple injuries and central nervous system damage is confirmed by our data, veryfying reports by Davis et al [6] of a 70 percent or greater mortality rate among comatose patients hospitalized with multiple trauma.

CO2 laser excision of pediatric airway lesions.

Treatment of life-threatening pediatric airway lesions has been greatly enhanced by development of the CO2 laser. Using this modality, endoscopic access and precise tissue destruction are possible with minimal local inflammation and subsequent edema of the narrow airway. From October 1986 through October 1988, 26 patients underwent 96 laser procedures for excision of airway lesions, in 23 patients via bronchoscopy and in three patients via microlaryngoscopy. Ages ranged from 1 day to 20 years, with most patients under 2 years of age. Diagnoses included: laryngeal cysts (1); cystic hygroma (3); tumor (neurofibroma, 1) subglottic hemangioma (1); excision of airway granulation tissue (8); and tracheal stenosis (13, including subglottic stenosis in 9). Therapy of the offending lesion required from one to eight laser procedures (mean, 2.8), excluding one patient with congenital long-segment tracheal stenosis who required 24 laser treatments for repeated excision of tracheal granulation tissue. Most lesions responded to only one or two laser treatments. No bleeding or perforation occurred secondary to laser use. Use of the laser was responsible for salvaging the airway or simplifying management of the airway in 21 of the 26 patients. In three patients with cystic hygroma affecting the laryngeal structures as well as soft tissues of the neck, laser excision was performed to maintain upper airway patency with a tracheostomy for airway control. Two patients with critical subglottic stenosis initially responded to laser excision, but moved away from the area and developed recurrence of their subglottic stenosis requiring tracheostomy, because further laser treatment was either unavailable or was deferred in their new locale.(ABSTRACT TRUNCATED AT 250 WORDS)

The venocutaneous fistula--a new approach to chronic venous access.

A surgical technique has been devised for creating access to the central venous circulation, yet avoiding a chronic, in-dwelling central venous catheter. While far removed from actual clinical application, the possibility of catheter-free access to the central venous circulation offers great potential for ease of care and a lessened infection rate of catheter-related sepsis.

Subcutaneous bronchogenic cysts.

Recent experience with a bronchogenic cyst occurring in a subcutaneous suprasternal location presents an additional entity to be considered in the differential diagnosis of head and neck lesions, and correlates with the embryology of the developing tracheobronchial tree and sternum. A review of subcutaneous bronchogenic cysts shows 41 cases have been described in the English literature. Most were noted in the suprasternal location; all but one were first noted in infancy or childhood. There is a definite male predominance. Sinus tracts were present in four cases, but none extended into the chest or mediastinum. Although local excision led to cure in all cases, incomplete excision in two cases required reoperation. Embryologic maldevelopment is suggested as the etiology for subcutaneous bronchogenic cysts, with a "pinching off" of pulmonary parenchyma by closure of the developing lateral sternal bars, fusion of which results in an isolated bronchogenic cyst in the subcutaneous tissues of the anterior chest wall. Awareness of this lesion by pediatric surgeons in the differential diagnosis of masses or sinuses presenting in the suprasternal region may prevent incomplete excision of components, which can extend deep into the site of origin. The possibility of extension into the mediastinum should be entertained.

Pediatric surgery in Bangladesh.

Bangladesh, although a small country of only 55,000 square miles, is the world's eighth most populous nation, and its 90 million inhabitants occupy a land of harsh economic conditions. One half of this dense population is children, 90% of whom suffer from parasitic infestations, 10% are affected with neonatal tetanus, and one half are severely malnourished. Health care resources are scarce with one physician and hospital bed for about every 10,000 persons. A 1-month stay in Bangladesh at the Dhaka Shishu Hospital, made possible by the Canadian Association of Paediatric Surgeons, afforded an invaluable opportunity to be involved in Pediatric Surgery in such a setting. During the month, over 40 major pediatric surgical procedures were performed, including sequestrectomy, drainage of parietal wall abscess, and resection of massive neoplasms. Many unusual pathologic conditions, not commonly seen in Western countries, were encountered including canker otis, tuberculous ileitis, and ascaris-induced small bowel obstruction. In the setting of widespread malnutrition and limited diagnostic aids, appropriate surgical treatment remains crucial in many serious childhood conditions. Awareness of some of the more unusual infections and parasites seen in Third World nations is of great importance to Western surgeons due to increased travel and immigration and for a perspective on diseases rarely seen in more affluent countries.

Spinning the wheels: a CAPS survey of ethical issues in pediatric surgery.

To evaluate decision-making factors of pediatric surgeons when faced with ethical dilemmas in a clinical setting, questionnaires were mailed to members of the Canadian Association of Paediatric Surgeons. The surgeons were asked to respond to scenarios regarding ethical dilemmas in the treatment of children. Fifty-one responses (57%) were computer analyzed based on chosen responses to the clinical dilemma and demographic factors such as age, sex, marital status, country of citizenship, religion, and "religiousness," a determination of religious conviction as viewed by the respondent. In addition, ethical convictions were sought regarding abortion, fetal research, AIDS, HIV testing, denial of medical care due to religious beliefs (Jehovah's Witness), and limitations in health care access for indigents. In general, respondents found it difficult to separate ethical guidelines for determining aggressive treatment--absolute value of life; best interests of the child; parental authority; and ability of the child to engage in social, intellectual, or emotional attachments (quality of life)--in the face of actual patient care issues. In fact, results of this survey indicate that the operating surgeon applies his/her medical knowledge and surgical "experience" to each individual case, incorporating his or her own ethical beliefs (in a respondent's words: "In the operating room, the surgeon must satisfy his own conscience in making decisions") while cognizant of legal guidelines for "standard care" ("Decisions would be based on personal experience, and what the local society believes to be right").(ABSTRACT TRUNCATED AT 250 WORDS)

Anterior cricoid split for subglottic stenosis.

Subglottic stenosis is a common problem that often results from ventilatory support necessary in the premature infant. Previous methods of treatment include tracheostomy with dilatation of the stenosis, steroid injections, and procedures to stent the trachea. Results of these methods have been unsatisfactory because of the multiple procedures needed to obtain an adequate airway as well as the high mortality from long-term tracheostomy in infants. In the past 2 years, seven infants have undergone an anterior cricoid split for tight subglottic stenosis and airway obstruction. Of the seven patients, six were premature, five of whom required ventilatory support ranging from 4 to 30+ days. Each child presented in respiratory distress with symptoms present in five children from 1 to 11 months (mean 3.8) after birth. Bronchoscopy identified the site of obstruction in each case as subglottic, with a narrow lumen, usually less than 2.5 mm in diameter. Anterior cricoid split was performed at ages ranging from 2 to 11 months (mean 5.0). All children were extubated at 10 to 14 days and subsequently discharged home asymptomatic; none required postoperative tracheostomy. Complications developed in five children, including atelectasis, otitis media, phlebitis, and tracheocutaneous fistula in two, one of whom required operative closure. One child was rebronchoscoped at 3 weeks postoperatively for bronchospasm, which resolved on aminophylline. The subglottic trachea was normal. At follow-up ranging from 2 to 21 months (mean 8.3), no child has symptoms referrable to the subglottic region. In one patient, a brief period of respiratory distress recurred 3 months postoperatively due to tracheomalacia.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon dilatation of long-segment tracheal stenoses.

Although a rare anomaly, congenital tracheal stenosis is associated with a high mortality. Surgical approaches proposed for this life-threatening lesion have included resection of localized stenoses; tracheoplasty involving interposition of cartilage, periosteum, or pericardium via an anterior tracheal split; or esophageal anastomosis to a posterior tracheal split. None of these techniques have provided uniformly satisfactory results, and all entail significant morbidity associated with the tracheal anastomosis. We have used endoscopic balloon dilatation in four children with critical airway obstruction from long-segment tracheal stenoses. In each of these patients, symptoms began early in life (from 2 weeks to 6 months of age) and consisted of respiratory distress from upper airway obstruction or recurrent episodes of stridor and chest retractions requiring hospitalization. The location of the tracheal stenoses varied, involving the upper third, middle third, middle half, and distal half of the trachea in the patients encountered. At bronchoscopy, the lumen was judged to be less than or equal to 1 mm in three of these patients. Dilatation was accomplished using Gruentzig balloon catheters in sizes ranging from 3 mm to (eventually) 8 mm, and produced a posterior split in the complete tracheal rings responsible for the stenosis in all patients, resulting in great increases in airway lumen. All children were improved following balloon dilatation, and three are currently doing well at 2.5, 3.0, and 3.0+ years postdilatation. One infant eventually died of airway obstruction incurred by severe bronchomalacia distal to the tip of an endotracheal tube that had been passed to the carina after sequential balloon dilatations.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of persistent pediatric tracheostomal fistulas.

Decannulation of a tracheostomy generally results in spontaneous closure. Occasionally, epithelialization results in persistence of the fistula, which may be initially treated by local curettage or cautery. Failure of these methods constitutes an indication for surgical closure. Dissection of the entire tracheocutaneous tract permits fistula closure in juxtaposition to but outside the trachea and prevents any iatrogenic airway narrowing. Twelve patients have been so managed over the last 10 years, and there have been no immediate or long-term complications.

Long-term venous access using endogenous splenic tissue: the 'spleen-o-port'.

The authors sought to determine whether endogenous splenic tissue placed in a subcutaneous pouch ("spleen-o-port") could function as a viable alternative to central venous catheters/ports for long-term venous access. A small transverse incision was made in the left upper quadrant of each puppy (n = 6) under general anesthesia. Using a stapler, the authors divided the splenic parenchyma. The superior portion was returned to its native location, and a subcutaneous pocket was created to house the inferior pole with its attached vascular supply. The fascial and muscular layers were closed with care to avoid compressing the blood supply to the spleen-o-port. Postoperatively the dogs resumed normal activity. There have been no deaths, infectious complications, splenic ruptures, or thromboses over a 6-month period. Under fluoroscopy, the dogs were imaged from postoperative day (POD) 10 to 177. Contrast agent entering the splenic parenchyma was promptly visualized in the splenic vein and then filled the portal vein. Electrolyte measurements from spleen-o-port blood samples were identical to those from peripheral venous samples. After gentamicin (mixed in a crystalloid solution) was infused through the spleen-o-port, the peak serum level corresponded to the therapeutic levels observed after standard intravenous administration. The spleen-o-port permits rapid infusion of drugs and crystalloid, and allows repetitive blood sampling while eliminating the foreign body that can promote septicemia in the immunocompromised patient.

Pseudomembranous colitis following resection for Hirschsprung's disease.

Enterocolitis is the most common cause of significant morbidity and death in Hirschsprung's disease. Although most cases respond to nasogastric decompression, antibiotics, and colonic evacuation, some children have an unusually fulminant or protracted clinical course. Four cases are reported of pseudomembranous colitis (PMC) that developed 1 to 18 months (mean, 8 months) after definitive surgery for Hirschsprung's disease (Soave endorectal pull-though, 2; Duhamel procedure, 2). While all children presented with fever, abdominal distention, and diarrhea, indistinguishable from typical Hirschsprung's enterocolitis, the clinical course was fulminant in two cases, both of whom died of septic shock. Postmortem examination in both showed extensive colonic pseudomembranes despite identification of Clostridium difficile toxin and subsequent vancomycin therapy (initiated late in the clinical course). Two children in the series had protracted hospitalizations and eventually required diverting enterostomy despite recognition of C difficile toxin and treatment with enteral vancomycin, in one child necessitating multiple courses of antibiotic therapy. Awareness of the virulence of PMC associated with Hirschsprung's disease (even after definitive resection) should prompt submission of stool specimens from any child who presents with enterocolitis for both C difficile culture and toxin levels. On the basis of our experience it is our policy to initiate a prompt course of vancomycin by rectal lavage or nasogastric tube in all children with Hirschsprung's enterocolitis, pending culture results, in view of the significant morbidity and mortality exemplified by cases in this review.

Potentially lethal complications of central venous catheter placement.

BACKGROUND: Placement of central venous catheters, although often considered to be a relatively safe and "junior"-level procedure, may be associated with life-threatening complications. METHODS: A recent surgical death associated with placement of a central venous catheter at this Institution led to submission of a questionnaire to pediatric surgeons referenced through the American Pediatric Surgical Association directory regarding knowledge of similar incidents and information regarding catheter placement-related complications. RESULTS: Results to this response, although anecdotal, provided data regarding complications of an acute nature, which fell into the categories of pneumothorax, hydrothorax, cardiac tamponade, and hemothorax. Of 10 children with cardiac tamponade, 7 were infants, and most complications were associated with needle stick for access, with symptoms developing within minutes up to 12 hours after the procedure. Drainage of the tamponade was performed by aspiration alone in 3 cases; surgical drainage in 6 children resulted in survival in 9 of the 10 patients. Hemothorax was described in 19 patients and appeared to be more common in children in the 1- to 6-year age group, usually associated with percutaneous access techniques. Thoracotomy for hemothorax was performed in 16 children with 11 survivors. Vascular injury to subclavian artery, vein, or superior vena caval were noted in most at operation. CONCLUSIONS: Although data included in this review are entirely anecdotal and not subject to scientific scrutiny or analysis, certain conclusions appear evident. Inherent risks of central venous catheters are intrinsic and should be discussed with the family in obtaining preoperative consent, including life-threatening risks that may necessitate urgent surgical intervention (by thoracotomy or other means). Certain technical aspects of the procedure should be rigidly followed with an experienced surgeon in attendance throughout the procedure. Rapid evaluation should be performed for any unexplained problems that occur in the operating theatre or during the early postoperative period.

Parathyroid cysts: report of the sixth and youngest pediatric case.

A nonfunctioning parathyroid cyst occurred in an 8-year-old girl, the youngest patient reported to have this diagnosis. Most cysts are asymptomatic; a few are associated with signs and symptoms of hyperparathyroidism. In asymptomatic patients with a lateral neck cyst, aspiration of clear fluid with an elevated parathyroid hormone level is diagnostic of a parathyroid cyst. If this results in disappearance of the cyst, without recurrence, no further treatment is necessary. If the cyst recurs, aspiration may be repeated. However, persistence of the cyst despite aspiration or recurrence after the second aspiration should prompt surgical removal, with intraoperative identification of all parathyroid glands, because functioning parathyroid cysts are associated with a high risk of hyperplasia or adenoma.

Myofibroblast induction with transforming growth factor-beta1 and -beta3 in cutaneous fetal excisional wounds.

BACKGROUND/PURPOSE: In a noncontractile fetal rabbit model, the authors recently have shown the induction of excisional wound contraction with sustained-release cellulose implants formulated with transforming growth factor (TGF)-beta. The purpose of this study was to test the hypothesis that the excisional wound contraction in this model is associated with the induction of myofibroblasts in the surrounding dermis, demonstrated by the presence of alpha-smooth muscle actin. METHODS: Cellulose discs were formulated with either 1.0 microg of TGF-beta1 (n = 6); 1.0 microg of TGF-beta3 (n = 9); 10 microg of TGF-beta3 (n = 6); or their carrier protein, bovine serum albumin (BSA; n = 9), for sustained-release over 5 days. Each disc was implanted into a subcutaneous pocket on the back of a fetal New Zealand White rabbit in utero on day 24 of gestation (term, 31 days). A full-thickness, 3-mm excisional wound (7.4 mm2) was then made next to the implanted cellulose disc. All fetuses were harvested at 3 days. The amount of alpha-smooth muscle (SM) actin in the dermis around the implants and wounds was determined using immunohistochemical techniques. RESULTS: Excisional wounds exposed to 1.0 microg of TGF-beta1 (5.6+/-2.0 mm2), 1.0 microg of TGF-beta3 (6.9+/-1.0 mm2), and 10 microg of TGF-beta3 (2.7+/-1.0 mm2) were significantly smaller when compared with the BSA control group (12.8+/-1.1 mm2; P<.05). Furthermore, there was a significant increase in staining for alpha-SM actin in the TGF-beta1 (1.8+/-0.5) and 10 microg TGF-beta3 (2.8+/-0.2) groups in comparison with the scant staining in the BSA control group (0.5+/-0.2; P<.05). CONCLUSIONS: TGF-beta1 and -beta3 induce alpha-SM actin and contraction of cutaneous excisional wounds in a fetal noncontractile model. This model of inducible cutaneous excisional wound contraction may be useful in further determining the role of the myofibroblast in wound contraction and the physiology underlying this poorly understood aspect of wound healing.

Preoperative staging, prognostic factors, and outcome for extremity rhabdomyosarcoma: a preliminary report from the Intergroup Rhabdomyosarcoma Study IV (1991-1997).

BACKGROUND: During the fourth Intergroup Rhabdomyosarcoma (RMS) Study (IRS IV, 1991-97), a preoperative staging system was evaluated prospectively for the first time. The authors evaluated this staging system and the role of surgery in extremity RMS in contemporary multimodal therapy. METHODS: A total of 139 patients (71 girls; median age, 6 years) were entered in IRS IV with extremity-site RMS. Stage was assigned by the IRSG Preoperative Staging System. Postsurgical group was determined by tumor status after initial surgical intervention. Multivariate analysis was performed using all pretreatment factors that were significant by univariate analysis, including clinical Group (i.e., I through IV), tumor invasiveness (T1,T2), nodal status (N0,N1), and tumor size (< or > or =5 cm). Failure-free survival rates (FFS) and survival rates were estimated using the Kaplan and Meier method. RESULTS: Preoperative staging and clinical group distribution were as follows: Stage 2, n = 34; Stage 3, n = 73; Stage 4, n = 32; Group I, n = 31; Group II, n = 21; Group III, n = 54; Group IV, n = 33. Three-year FFS was 55%, and the overall survival rate was 70%. Eighty-seven patients had either unresectable, gross residual disease (Group III) or metastases (Group IV). FFS was significantly worse for these patients with advanced disease, compared with that for patients with complete resection or with only microscopic residual tumor (i.e., Group I or II; Group I, 3-year FFS, 91%; Group II, 72%; Group III, 50%; Group IV, 23%; P<.001). Lymph nodes were evaluated surgically in 76 patients with positive results in 38. Clinically, 13 additional patients had nodal disease. Both stage and group were highly predictive of outcome and were highly correlated. By multivariate analysis, none of the other variables were predictors of FFS. CONCLUSIONS: This review confirms the utility of pretreatment staging for stratification of patients with extremity RMS with widely different risks of relapse, thereby paving the way for development of risk-based therapy. Group (operative staging) remains the most important predictor of FFS, emphasizing the importance of complete gross resection at initial surgical intervention, when feasible without loss of limb function. The high incidence of nodal disease in the patients who had lymph node biopsy confirms the need for surgical evaluation of lymph nodes to ensure accurate staging in children with extremity rhabdomyosarcoma.