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Purpose: Tubular secretion of cisplatin is abolished in mice deficient for the organic cation transporters Oct1 and Oct2 (Oct1/2(-/-)mice), and these animals are protected from severe cisplatin-induced kidney damage. Since tubular necrosis is not completely absent in Oct1/2(-/-)mice, we hypothesized that alternate pathways are involved in the observed injury., Experimental Design: Studies were done in wild-type, Oct1/2(-/-), or p53-deficient animals, all on an FVB background, receiving cisplatin intraperitoneally at 15 mg/kg. Cisplatin metabolites were analyzed using mass spectrometry, and gene expression was assessed using Affymetrix microarrays and RT-PCR arrays., Results: KEGG pathway analyses on kidneys from mice exposed to cisplatin revealed that the most significantly altered genes were associated with the p53 signaling network, including Cdnk1a and Mdm2, in both wild-type (P = 2.40 × 10(-11)) and Oct1/2(-/-)mice (P = 1.92 × 10(-8)). This was confirmed by demonstrating that homozygosity for a p53-null allele partially reduced renal tubular damage, whereas loss of p53 in Oct1/2(-/-)mice (p53(-/-)/Oct1/2(-/-)) completely abolished nephrotoxicity. We found that pifithrin-α, an inhibitor of p53-dependent transcriptional activation, inhibits Oct2 and can mimic the lack of nephrotoxicity observed in p53(-/-)/Oct1/2(-/-)mice., Conclusions: These findings indicate that (i) the p53 pathway plays a crucial role in the kidney in response to cisplatin treatment and (ii) clinical exploration of OCT2 inhibitors may not lead to complete nephroprotection unless the p53 pathway is simultaneously antagonized., (©2014 American Association for Cancer Research.)

The macrolide antiobiotic erythromycin undergoes extensive hepatic metabolism and is commonly used as a probe for cytochrome P450 (CYP) 3A4 activity. By means of a transporter screen, erythromycin was identified as a substrate for the transporter ABCC2 (MRP2) and its murine ortholog, Abcc2. Because these proteins are highly expressed on the biliary surface of hepatocytes, we hypothesized that impaired Abcc2 function may influence the rate of hepatobiliary excretion and thereby enhance erythromycin metabolism. Using Abcc2 knockout mice, we found that Abcc2 deficiency was associated with a significant increase in erythromycin metabolism, whereas murine Cyp3a protein expression and microsomal Cyp3a activity were not affected. Next, in a cohort of 108 human subjects, we observed that homozygosity for a common reduced-function variant in ABCC2 (rs717620) was also linked to an increase in erythromycin metabolism but was not correlated with the clearance of midazolam. These results suggest that impaired ABCC2 function can alter erythromycin metabolism, independent of changes in CYP3A4 activity.

Purpose: This study aimed to test the influence of functional renal organic cation transporters (OCT2 in humans, Oct1 and Oct2 in mice) on biomarkers of cisplatin nephrotoxicity, such as urinary activity of N-acetyl-beta-D-glucosaminidase (NAG)., Experimental Design: Temporal cisplatin-induced nephrotoxicity was assessed by histopathology and biomarkers. Cisplatin-mediated NAG changes and survival were determined in wild-type and Oct1/2(-/-) mice. Identification of OCT2 inhibitors was done in transfected 293Flp-In cells, and the NCI(60) cell line panel was used to assess contribution of OCT2 to cisplatin uptake in cancer cells., Results: Classical biomarkers such as blood urea nitrogen and serum creatinine were not elevated until 72 hours after cisplatin administration and substantial kidney damage had occurred. Oct1/2(-/-) mice had 2.9-fold lower NAG by 4 hours (P < 0.0001) and 2.3-fold increased survival (P = 0.0097). Among 16 agents, cimetidine strongly inhibited uptake of tetraethylammonium bromide (P = 0.0006) and cisplatin (P < 0.0001), but did not have an influence on cisplatin uptake in SK-OV-3 cells, the cancer line with the highest OCT2 mRNA levels. In wild-type mice, cimetidine inhibited cisplatin-induced NAG changes (P = 0.016 versus cisplatin alone) to a degree similar to that seen in Oct1/2(-/-) mice receiving cisplatin (P = 0.91). Cumulative NAG activity of >0.4 absorbance units (AU) was associated with 21-fold increased odds for severe nephrotoxicity (P = 0.0017), which was linked with overall survival (hazard ratio, 8.1; 95% confidence interval, 2.1-31; P = 0.0078)., Conclusions: Cimetidine is able to inhibit OCT2-mediated uptake of cisplatin in the kidney, and subsequently ameliorate nephrotoxicity likely with minimal effect on uptake in tumor cells.

Objective: To determine the accuracy of a protocol for diagnosis of appendicitis in children based on clinical evaluation by a pediatric surgeon with selective use of diagnostic imaging studies. We performed this study because 1) current reports in the medical, pediatric, emergency medical, and surgical literature advocate imaging, particularly computed tomography (CT), as the gold standard for diagnosis of appendicitis, and 2) the value of pediatric surgical evaluation early in the management of the child with possible appendicitis has rarely been emphasized. METHODS, DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 356 children (mean age: 9.6 years; range: 1-18 years) referred to a regional pediatric surgical center for possible appendicitis from 1999 through 2001., Interventions: Initial pediatric surgical evaluation consisted of history, physical examination, white blood cell count, differential count, and urinalysis. Children diagnosed with appendicitis underwent appendectomy without additional studies; those with equivocal findings received intravenous fluids, rest, and reevaluation after 4 to 6 hours. Imaging was used selectively by the pediatric surgeon., Outcome Measures: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the protocol based on final diagnoses; rate of appendiceal perforation; and rate of negative appendectomy., Results: Of 356 children evaluated for appendicitis, 220 (62%) had an appendectomy. Two-hundred nine (95%) had histologically proven appendicitis, and 11 (5%) had a normal appendix. Of the 209 children with appendicitis, 139 (66%) had acute appendicitis, 34 (16%) had advanced appendicitis without perforation, and 36 (17%) had advanced appendicitis with perforation. Appendectomy was performed after initial evaluation in 195 (89%) of the 220 children and after a period of supportive care and observation in 25 (11%) of 220. One hundred thirty-six children (38%) did not have an appendectomy and were discharged with other diagnoses. The sensitivity of this protocol was 99%, specificity was 92%, positive predictive value was 95%, and negative predictive value was 99%. The accuracy was 97% compared with an accuracy of 82% for ultrasound alone and 90% for CT scan alone., Conclusions: These data show that a protocol based on clinical evaluation by a pediatric surgeon with selective use of imaging was highly accurate for the diagnosis of appendicitis in children. Low rates of negative appendectomy (5%) and perforation (17%) were achieved without the potential costs and radiation exposure of excess imaging.

Necrotizing enterocolitis (NEC), a syndrome characterized by crepitant necrosis of the bowel, has emerged as the most common neonatal gastrointestinal emergency in many countries of the world. In the United States, NEC strikes 1 to 8% of patients admitted to neonatal intensive care units, almost all of whom are premature infants. The incidence is low in certain countries wity a low premature birth rate, e.g., Japan. Two theories of pathogenesis are: the Santulli theory, which implicates three factors: ischaemia, bacteria and substrate; and the Lawrence theory, which stresses the injurious role of bacterial toxins on the immature gut of the preterm infant. Clinical and experimental evidence support each of the theories, but neither theory can explain certain clinical phenomena, particularly the resistance to NEC manifested by more than 90% of preterm infants, who never develop the syndrome. A unifying hypothesis of pathogenesis and a mathematical model of NEC are outlined. Because clustering of cases may occur, the design of clinical trials of preventive measures for NEC must include simultaneous control infants., (Copyright © 1997 Published by Elsevier Ltd.)

Unlabelled: Necrotizing fasciitis (NF) is a bacterial infection of the soft tissues with a fulminant course and a high mortality rate. The authors performed a review to define the diagnosis, bacteriology, and management of NF in the pediatric population. This report of 20 cases treated over 18 years represents the largest reported pediatric experience. These infections were attributable to secondary infection of varicella lesions (5), omphalitis (4), extremity lesions (4), perineal infections (3), head and neck lesions (2), inguinal herniorrhapy (1), and breast abscess (1). Nineteen of the 20 children were healthy, without chronic disease or immunosuppression. All patients presented with an altered sensorium and signs of systemic toxicity. Fever (40%), tachycardia (70%), and abnormal white blood cell count (50%) were not uniformly present. There was marked tissue edema in all patients, with a characteristic peau d'orange appearance in 18. Seven infections were caused by streptococcus; the remainder were polymicrobial, involving multiple aerobes and anaerobes. Initial gram stain was of limited utility; in 14 of 19 cases the result was negative or showed only one of many organisms present. Fifteen patients survived and five died. All survivors underwent aggressive surgical debridement within 3 hours of admission. The survivors required of a mean of 3.8 operations. Fascial excision of up to 35% of total body surface area was required. One patient required amputation, two had colostomies, and six required extensive skin grafting for reconstruction. All five patients who died had delayed initial management., Conclusion: NF is a serious cause of death in previously healthy children. The diagnosis should be considered in the presence of any soft tissue infection presenting with signs of toxicity and marked wound edema, even in the absence of fever or abnormal white blood cell count. Immediate surgical debridement and coverage with penicillin, an aminoglycoside, and metronidazole are essential. Subsequent changes in antibiotics should be based on culture data because gram stain results are not reliable. More than one operation is required in almost all cases.

Infection remains a major cause of death and complication in pediatric surgery today. Impaired host resistance from such circumstances as immaturity, cancer chemotherapy, or AIDS predisposes to opportunistic infection by fungi, viruses, mycobacteria, and even protozoa. This review considers recent advances in five areas: 1) sepsis, 2) soft-tissue and wound infections, 3) chest infections, 4) abdominal infections, and 5) miscellaneous (including nosocomial) infections. Of particular importance are the new concepts of sepsis. The new terminology distinguishes stages in the septic process and a complex interaction of inflammatory mediators. The systemic inflammatory response syndrome may progress independently of the original infection to multiorgan dysfunction syndrome, and death. The reports cited herein are, for the most part, retrospective observational studies. There is a great need for prospective, randomized trials to answer questions about the optimal management of, and prevention of, pediatric surgical infections.

Operation for necrotizing enterocolitis (NEC) is reserved for infants with intestinal gangrene or perforation. It should not be undertaken until gangrene is present, but ideally should be performed before intestinal perforation occurs. To characterize the onset of intestinal gangrene, data were analyzed for 147 infants with documented NEC, 94 of whom had gangrene. Twelve criteria were evaluated as predictors of intestinal gangrene, using standard epidemiological measures for diagnostic tests. Sensitivity, specificity, positive predictive value, negative predictive value, and prevalence were calculated for each of the proposed operative criteria. The best indications were those whose specificity and positive predictive value approached 100%, and whose prevalence was greater than 10%. These were pneumoperitoneum, positive paracentesis, and portal venous gas. Good indications were those whose specificity and positive predictive value approached 100%, but whose prevalence was less than 10%. These were fixed intestinal loop noted on x-ray, erythema of the abdominal wall, and a palpable abdominal mass. A fair indication for operation--with 91% specificity, 94% positive predictive value, and prevalence of 20%--was "severe" pneumatosis intestinalis, graded by a radiographic system. Poorer indications for operation (and their predictive value for the presence of gangrene) were clinical deterioration (78%), platelet count below 100,000/mm3 (73%), abdominal tenderness (58%), severe gastrointestinal hemorrhage (50%), and gasless abdomen with ascites (0%). No test had a high sensitivity for intestinal gangrene. Portal venous gas should be acknowledged as an indication for operation. Probability analysis may provide a more scientific basis for clinical decision-making.

The management of pediatric empyema remains controversial. An experimental study was undertaken to evaluate the role of bacteria in the evolution and severity of empyema, using specific bacteria that are pathogens of empyema in children. A rabbit model was used. The groups were Haemophilus influenzae (n = 9), Bacteroides fragilis (n = 8), the combination (n = 12), Staphylococcus aureus (n = 6), and control (n = 6). The total bacterial inoculum (10(8)) was constant. Diagnostic thoracentesis was performed at regular intervals. Characteristics of the empyema were evaluated when the rabbits were killed (at 4, 7, and 10 days). Most rabbits other than those of the mixed-bacteria group cleared the bacteria from their pleural cavities. Eleven of 12 mixed-bacteria animals had multiloculated empyemas; only one resolved spontaneously. In the other groups, the tendency was toward unilocular empyemas, which resolved by the 10th day in one third of the H influenzae animals, two thirds of the Bacteroides fragilis animals, and half the S aureus animals. The empyemas that persisted until the 10th day were in the exudative or fibrinopurulent stage, except for those of the mixed-bacteria group, all of which were in the advanced organizing stage. The amount of pleural debris and the degree of organization were significantly greater for the mixed bacteria group (P > .01). These findings support the clinical management of monobacterial empyema by simple drainage, whereas mixed aerobic-anaerobic empyemas may require more aggressive drainage procedures.

Pulmonary sequestration is a mass of abnormal pulmonary tissue that does not communicate with the tracheobronchial tree and is supplied by an anomalous systemic artery. Whereas extralobar sequestration is clearly congenital, intralobar sequestration, which frequently presents in older children with pathological findings showing acute and chronic inflammation, may have an acquired origin secondary to frequent infections. Several large autopsy series support an acquired etiology of intralobar sequestration. Four cases of intralobar sequestration are presented that demonstrate a spectrum of inflammatory change that support its congenital, rather than acquired origin. Case 1 was a newborn who presented with tachypnea and a right lower lobe density. Resection at 3 weeks of age showed no inflammation in the sequestration specimen. Case 2 presented as a newborn infant with congestive heart failure. Pulmonary sequestration was confirmed by arteriogram. Resection at 3 months of age showed chronic inflammation. Case 3 presented at 7 months of age with chronic pneumonia. The resected specimen demonstrated moderately severe acute and chronic inflammation. Case 4 presented as a 6 year old. The operative specimen showed extensive bronchiectatic changes with marked acute and chronic inflammation. These cases support the congenital origin of intralobar sequestration and suggest a temporal progression from no inflammation to severe acute and chronic inflammation.

We studied nosocomial infection in a group of 608 pediatric surgical patients over a 14-month period. All inpatients and outpatients who received an operation with an incision by the pediatric general surgical service were entered into the study. Demographic, nutritional, clinical, and laboratory data were collected. Surveillance was conducted for wound infection, septicemia, infections of the respiratory tract, urinary tract, and abdomen, and infectious diarrhea. A total of 676 operative procedures was performed. Nosocomial infection occurred in 38 of the 608 patients (6.2%). A total of 53 infectious complications was tabulated. The number and percent risk per operation were wound 17 (2.5%), septicemia 14 (2.1%), pulmonary 10 (1.5%), urinary tract 5 (0.7%), abdominal 5 (0.7%), diarrhea 2 (0.3%). Broviac catheter sepsis occurred in 7 of 61 lines (11.5%). The highest overall occurrence of infection was in the infant group (1 mo to 1 yr), (13/161, 8.1%). The probability of septicemia was highest in neonates (4.2%) compared with infants (3.1%) or older children (1.2%) (P < .05). The most common isolates were Staphylococcus epidermidis (10/17) from septic patients, and gram-negative enteric bacteria (27/50) from organ and wound infections. Infection was associated with impaired nutrition, multiple disease processes, and multiple operations. The risk of nosocomial infection in this population was comparable to that reported in adult surgical patients. These baseline data may aid the development of strategies to lower infection risk in children.

One possible complication in infant pneumonectomy is mediastinal shift that can fatally kink or compress airways and vessels. Rigid prostheses have been used to prevent these problems; however, they cannot be adjusted as the child grows. We report a case of expandable prosthesis implantation in a 24-day-old infant. During the 18 months postimplantation, the prosthesis was periodically injected with a saline/contrast solution to maintain the mediastinum in a midline position as the child grew. At 24-month follow-up the prosthesis was still in place, and midline position of the mediastinum maintained.

The operation of a neonate with periumbilical necrotizing fasciitis consisted of (1) excision of infected skin, fat, and fascia (including the umbilicus); (2) a limited laparotomy, with ligation and excision of the umbilical vessels and urachal remnant; and (3) placement of a temporary silastic patch over the central abdominal defect. Pathological sections confirmed the spread of infection along the vessels and urachal remnant. Excision of the vessels and urachal remnant may be crucial to survival from periumbilical necrotizing fasciitis.

Severe bronchomalacia occurred in a 14-month-old boy, as a result of compression of the left mainstem bronchus by a bronchogenic cyst. After resection of the cyst, the bronchomalacia was corrected by suspension of the posterolateral bronchial wall to the ligamentum arteriosum. This method of bronchopexy may be of value for severe left mainstem bronchomalacia.

We analyzed our experience with 64 infants with esophageal atresia (EA) and tracheoesophageal fistula (TEF), to determine the possibility of prediction and prevention of anastomotic complications (leak, stricture, and recurrent TEF). In most of the infants, the anatomical level of the fistula was documented preoperatively by bronchoscopy. The level of the fistula, in turn, correlated with the esophageal anatomy at thoracotomy, ie, carinal fistulas had a wide gap between esophageal pouches, whereas midtracheal or cervical fistulas had a minimal gap. Major anastomotic complications were defined as leak requiring reoperation, symptomatic strictures requiring four or more dilatations, or a recurrent TEF. The complication rates wre: leak (major and minor), 21%; major stricture, 15%; and recurrent TEF, 5%. Major complications occurred in 42% (11/26) of infants with wide gaps, compared with 8% (3/36) of infants with minimal gaps. Route of repair (transpleural or retropleural) made no difference in incidence of anastomotic complications. No infant died of an anastomotic complication. Survival was 100% for Waterston A and B infants, 83% for Waterston C, and 90% overall. Severe gastroesophageal reflux, requiring Nissen fundoplication, was more common among infants with wide gaps than those with minimal gaps (32% v 3%). The most important pathogenetic factor, present in 79% (11/14) of major anastomotic complications, was anastomotic tension, determined by the gap between esophageal pouches, and predicted by preoperative bronchoscopy. Thus the bronchoscopic finding of a carinal fistula signals the need for technical measures that may limit anastomotic morbidity, such as myotomy, patching the anastomosis, retropleural approach, or delayed repair. Assuming precise technique and gentle handling of tissues, the anatomy of the anomaly determines the anastomotic morbidity of EA and TEF.

A tissue flap of azygous vein was successfully used for reinforcement of the esophageal anastomosis in two infants with wide-gap esophageal atresia and carinal tracheoesophageal fistula. In spite of anastomotic tension, both esophagi healed without leak or stricture. This technique may be of value in the surgical correction of esophageal anomalies.

We conducted an epidemiologic study of postoperative wound infection in pediatric patients. Over a 14-month period, 676 patients who received an operative incision on the Pediatric Surgical service were entered. Demographic, nutritional, clinical, and laboratory data were collected. The patients were followed for development of postoperative wound infection. Cultures were taken from wounds to identify the offending organisms. Of the 676 patients, 137 were neonates, 197 infants, and 342 older children. Wound infection occurred in 17 patients (2.5%): 1 neonate (0.7%), 8 infants (4.1%), and 8 older children (2.3%). Infection rates according to wound classification were: clean 1.0%, clean-contaminated 2.9%, contaminated 7.9%, and dirty 6.3%. Heavily contaminated or dirty wounds were packed open in one third of cases, and allowed to heal by granulation. The largest group of wound infections followed operations on the gastrointestinal tract (10 patients, 267 operations, 3.7%). Staphylococcus aureus, Escherichia coli, and alpha hemolytic streptococcus were the most common wound pathogens. An increased rate of wound infection was associated with operative procedures longer than 1 hour, with the presence of an associated illness, and with emergency operations. Age, sex, nutritional status, and duration of preoperative hospital stay did not significantly alter the wound infection rate. It could be concluded that the incidence of wound infection was lower among pediatric surgical patients than the reported incidence in adult surgical patients. The greatest risk factors were those associated with local contamination of the surgical wound.

Necrotizing enterocolitis is the most common gastrointestinal emergency in the newborn. The syndrome strikes premature infants during the first 2 weeks of life. Abdominal distention, lethargy, and feeding intolerance are early signs of NEC that may progress to gastrointestinal bleeding and hemodynamic instability. The radiographic hallmark of NEC is pneumatosis intestinalis (air in the bowel wall). The ileum and colon are the usual sites of crepitant intestinal necrosis, leading frequently to perforation. In spite of appropriate medical therapy, about half of the infants with NEC develop intestinal gangrene or perforation and require surgery, consisting of bowel resection and enterostomy formation. The most common late complication, intestinal stricture, occurs in 15 to 35 per cent of recovered infants. Overall mortality from NEC ranges from 20 to 40 per cent. The etiology of NEC is poorly understood and is considered to be multifactorial, related to ischemia, bacterial colonization, and formula feedings in a susceptible infant. Future progress in the treatment of NEC may be achieved by earlier detection of necrosis, modification of gastrointestinal flora, or by bolstering the deficient gastrointestinal immune mechanisms of the premature neonate.

After resolution of acute necrotizing enterocolitis (NEC), six of 31 surviving infants (19%) developed late ischemic stricture of the colon. Stricture occurred after both medical and surgical treatment for NEC, and in both functional and defunctionalized bowel. In medically-treated infants, the symptoms of intestinal obstruction usually began six to eight weeks after NEC. Surgically-treated infants developed asymptomatic strictures distal to an enterostomy. Barium enema was the appropriate diagnostic study for both groups. Operative management consisted of segmental colonic resection with frequent use of enterostomy. On histopathologic examination, resected strictures showed a spectrum of the reparative process after intestinal ischemia, ranging from obliterative scar to near-normal colon. Because delayed diagnosis led to the death of one of our infants, we recommend a barium enema for early diagnosis of stricture about six weeks after NEC, whether initial treatment was medical or surgical. In a recent infant, two colonic strictures were thus diagnosed and resected prior to development of symptoms of intestinal obstruction.

Two girls, aged 3 and 6 years, were treated for precocious pseudopuberty associated with a follicular ovarian cyst. Both patients had breast enlargement, areolar pigmentation, and elevated serum estradiol levels. In one girl, a normal displaced uterus was palpated; in the other, an ovarian cyst was identified by ultrasonography. Surgical treatment consisted of limited resection of the follicular cysts. Rapid regression of breast hypertrophy and return of estradiol levels to normal occurred in both children, who were followed for six and 1.5 years. We believe that a conservative operation that preserves normal ovarian tissue bilaterally is the procedure of choice for treating this condition.

New instruments and techniques have refined the art of extracting aspirated foreign bodies from children. During a five-year period at the University of New Mexico, Albuquerque, bronchoscopic extractions were successful in 40 of 41 children (98%). The extractions were performed with the patient under general anesthesia, using a pediatric ventilating bronchoscope that contained the Hopkins rod-lens system. Two methods of extraction were used, depending on the shape of the foreign object: the Fogarty balloon technique for spherical objects, and the forceps technique for flat objects. Using these techniques, most foreign bodies (80%) were removed on the first or second pass of the bronchoscope. Because bronchoscopic extraction is a delicate procedure and carries a risk of cardiorespiratory arrest, it should be performed by endoscopists and anesthesiologists who are skilled with this procedure in children.

A study to evaluate peritoneal fluid as an index of intestinal gangrene in infants with necrotizing entercolitis (NEC) was begun in 1974. Twenty samples of peritoneal fluid were obtained by paracentesis or lavage from 15 infants with nonperforated NEC. A brown color in the peritoneal fluid was noted in all 8 patients found to have intestinal gangrene at subsequent operation. Gram stain showed bacteria in 6 of these 8 patients and bacterial cultures were confimatory in all but one. In 12 samples of peritoneal fluid in patients without intestinal gangrene, the fluid was straw-colored or pink and Gram stain showed no bacteria. The decision to operate on an infant with intestinal gangrene and impending perforation may be aided by analysis of the peritoneal fluid.

5 infants with no growth of bacteria on cultures of blood and peritoneal fluid recovered from necrotising enterocolitis after medical treatment alone. 12 infants with positive cultures required surgery. 5 of these 12, who did not harbour clostridia, had a mild clinical course and all 5 survived segmental bowel resection. The 7 infants who harboured clostridia had a more severe clinical course and 4 died. In 3 of 4 infants with Clostridium perfringens, the necrotising enterocolitis was fulminant, characterised by severe pneumatosis intestinalis, extensive gangrene, early intestinal perforation, and a fatal outcome.

Grüntzig balloon catheters were used to dilate ten esophageal strictures in eight infants and children. Five infants who had anastomotic strictures following esophageal atresia repair gained complete resolution of their strictures, usually after one or two dilatations. Three older children who had strictures following esophageal re-operation or reconstruction required longer courses of dilatations to achieve consistent esophageal patency. The technique failed in two chronic strictures of two and one-half and nine years' duration. Balloon catheter dilatation, begun in the early postoperative period, is a safe, effective method for dilating esophageal strictures.

The case of a 5-year-old girl with a giant cystic hygroma of the posterior mediastinum is reported. Although the tumor was bilateral, it was excised by unilateral thoractomy. The unique anatomical features of this tumor suggested an embryologic origin from the cisterna chyli or the primitive paired thoracic ducts.

A study to evaluate criteria for operation was carried out in 61 infants with acute necrotizing enterocolitis (NEC). A total of 10 clinical, roentgenographic, and laboratory criteria were considered. Each proposed operative criterion was correlated with the documented presence or absence of intestinal gangrene in these infants. Indications for operation verified by this study were (1) pneumoperitoneum, (2) paracentesis findings positive for gangrenous intestine, (3) erythema of the abdominal wall, (4) a fixed abdominal mass, and (5) a persistently dilated loop of intestine on serial abdominal radiographs. The first two signs occurred frequently; the latter three were rare. Operative indications which proved to be invalid in this study were (1) clinical deterioration, (2) persistent abdominal tenderness, (3) profuse lower gastrointestinal hemorrhage, (4) the roentgenographic finding of gasless abdomen with ascites, and (5) severe thrombocytopenia. Twenty-four of the infants were operated on. The mortality rate among the infants operated on after free intestinal perforation had occurred (64%) was double that of infants operated on for intestinal gangrene without perforation (30%). Paracentesis may identify infants with intestinal gangrene prior to the development of perforation and may permit advantagenous timing of operation. This analysis of the frequency and reliability of proposed operative criteria may aid the surgical decision.

The efficacy of the inhalation-postural drainage technique for removal of aspirated foreign bodies was compared with that of bronchoscopy in 76 children. Twelve of 49 children on postural drainage coughed out the foreign body (25%); the other 37 required bronchoscopy. The foreign body was successfully removed in 56 of 63 children who were bronchoscoped (89%). Our experience suggests that a trial of inhalation-postural drainage, administered in a hospital, may be valuable in the initial management of aspirated foreign bodies. If unsuccessful after several treatments, however, the technique should be abandoned, and bronchoscopy performed. Delay of foreign body removal beyond 24 hours may be associated with increased morbidity and prolonged hospital stay. With recent improvements in pediatric endoscopic instruments, the efficacy of bronchoscopy exceeds 90%.

Creation of a substitute hemidiaphragm for an infant born with agenesis of the hemidiaphragm is a formidable task. Subsequent growth of the infant may produce distortion or fracture of diaphragmatic prostheses. Our experience with a surviving two year old infant with agenesis led us to conclude that a Silastic prosthesis is unsatisfactory and that a polypropylene mesh prosthesis is satisfactory as a diaphragmatic substitute.

This study was undertaken to evaluate the relative contribution of ischemia, bacteria, and luminal substrate, the pathogenetic components of necrotizing enterocolitis (NEC), to the development of intestinal necrosis. Sprague-Dawley rats, either germ-free (No. = 25) or conventionally colonized (No. = 20) underwent laparotomy. Isolated ileal segments were created, two per rat. Ischemia was produced in one segment by application of a microaneurysm clip; the other segment served as a control. Segments were injected with 1 mL of either normal saline, dilute Similac formula, or standard formula. Groups were as follows: Group I (germ-free), received saline; Group II (germ-free), dilute formula; Group III (germ-free), standard formula; Group IV (conventional), saline; Group V (conventional), dilute formula; Group VI (conventional), standard formula. At 48 hours, the rats were evaluated for survival, gross bowel integrity, histologic severity of necrosis (graded 0 to 4+), and bacteriology. Gross analysis of bowel integrity showed no lesions in the ischemic segments of the germ-free rats (Groups I, II, and III) and necrosis in 75% of conventionally colonized animals (Groups IV, V, and VI; P less than 0.001). Microscopic necrosis was more common (P less than 0.001) in ischemic segments of conventional rats than in ischemic segments of germ-free rats. There was no difference in necrosis attributable to ischemic time or to the presence of either standard or dilute formula. Of the three pathogenetic factors evaluated, the presence of bacteria was most crucial to the development of bowel necrosis in this model. Improved treatment and prevention of NEC may depend upon suppression and/or modification of the gut flora.

To investigate whether radiographic findings could be used to predict pan-necrosis (necrosis of 75% or more of the jejunum, ileum, and colon), we reviewed the serial abdominal radiographs and clinical records of 147 infants with necrotizing enterocolitis. Pan-necrosis occurred in 29 infants (20%) and was always fatal. The presence and degree of pneumatosis intestinalis, pneumoperitoneum and portal venous gas were studied. Pan-necrosis occurred least frequently in infants with mild or moderate pneumatosis intestinalis (8% and 12%, respectively), and with moderate frequency in those with pneumoperitoneum (33%). Pan-necrosis was found most frequently in infants with severe pneumatosis intestinalis (56%), portal venous gas (61%), or the combination of severe pneumatosis intestinalis and portal venous gas (79%). The mortality rates in these three groups were 63%, 65%, and 86%, respectively. Thus, infants with the worst outcome (those who develop pan-necrosis) can be identified on plain films by detection of severe pneumatosis intestinalis and portal venous gas.