Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

BACKGROUND: Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA). METHODS: We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher's exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes. RESULTS: 589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03). CONCLUSION: Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

CT imaging features of symptomatic and asymptomatic floating aortic thrombus.

AIM: To present the computed tomography (CT) imaging features of floating aortic thrombus with emphasis on clinical and radiographic predictors for systemic shower emboli. MATERIALS AND METHODS: A retrospective computerised search for patients with protruding thoracic aortic thrombus on CT was conducted. Clinical and demographic characteristics were retrieved from medical files. Patients were divided into two groups: symptomatic and asymptomatic, based on the presence or absence of documented systemic emboli at the time of diagnosis or during follow-up. CT imaging features were analysed: location and extent of systemic emboli, presence or absence of thrombus insertion calcification, percentage of thrombus circumference that is attached to the aortic wall and thrombus volume. Clinical and demographic variables and CT imaging features were analysed as potentially associated with symptomatic emboli. RESULTS: The symptomatic group included 6/15 (40%) patients and the asymptomatic group included 9/15 (60%) patients. Patients in the symptomatic group were significantly younger (symptomatic: 53.3±11.7 years, asymptomatic: 76.9±8.4 years, p=0.003). All the symptomatic patients were women (100%), while 2/9 (22.2%) of the asymptomatic patients were women, (p=0.007). A non-calcified insertion site was more frequent in the symptomatic group (symptomatic 4/6 [66.7%] versus asymptomatic group 1/9 [11.1%], p=0.011). The percentage of thrombus circumference attached to the aortic wall was significantly smaller in symptomatic patients (symptomatic: 31.8±8.4%, asymptomatic: 43.7±5%, p=0.003). CONCLUSION: The imaging features of symptomatic floating thrombus include a narrow base of attachment and lack of insertion calcification. Free-floating thrombus should be actively sought and diagnosed or excluded when performing CT andiography for emboli.

Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor.

BACKGROUND/PURPOSE: Antiangiogenic agents offer a new approach to the treatment of aggressive neoplasms, yet very few agents are available for current use. The authors have shown previously the efficacy of antiangiogenic therapy in experimental Wilms tumor, using an investigative antibody. They hypothesized that topotecan, administered in a regimen targeting endothelial cells, would suppress tumor growth and angiogenesis in experimental Wilms tumor. METHODS: Experimental tumors were induced in the left kidneys of athymic mice by injection of cultured Wilms tumor cells. Topotecan (0.36, 0.6, 1.0, 2.0, and 3.0 mg/kg) or vehicle was injected intraperitoneally in 2 cycles over a 6-week period. Fluorescein angiograms and platelet endothelial cell adhesion molecule-1 staining of primary tumors were performed to ascertain vascular architecture. Endothelial apoptosis was assessed by TdT-mediated dUTP nick end labeling assay. RESULTS: Tumor weights were reduced significantly in treated versus control animals, even in the lowest-dose group. Endothelial cell staining and angiography results showed relatively sparse vascularity in treated xenografts. Endothelial apoptosis was observed in treated but not control tumors. CONCLUSIONS: Topotecan, delivered in an "antiangiogenic" regimen, even at very low doses, significantly inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemotherapy agent topotecan may be useful in a novel role: as antiangiogenic therapy. J Pediatr Surg 36:1781-1784.

Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor.

BACKGROUND/PURPOSE: Antibody to vascular endothelial growth factor (anti-VEGF) suppresses tumor growth and metastasis in experimental Wilms tumor. However, tumor growth accelerates if antibody is withdrawn. As recently shown, low-dose, frequently administered topotecan, a topoisomerase-1 inhibitor, has anti-angiogenic activity. The authors hypothesized that combined topotecan/anti-VEGF therapy would suppress tumor growth and metastasis more durably than either agent alone. METHODS: Xenografts were induced by intrarenal injection of human Wilms tumor cells in athymic mice (n = 59). Mice were divided into control (n = 10), anti-VEGF (n = 16), topotecan (n = 17), and topotecan plus anti-VEGF (n = 16) groups. All control and half the treated mice were killed at week 6. Remaining ("rebound") mice were maintained without treatment until week 8. Tumor vasculature was mapped by fluorescein angiography/PECAM immunostaining. Endothelial apoptosis was assessed by TUNEL assay. RESULTS: 6 weeks: Tumor weights were reduced significantly in treated mice (P <.003 v control). Seven of ten control and 1 of 25 treated mice displayed lung metastases (P <.003). Rebound tumors were largest in topotecan-only, intermediate in antibody-treated, and smallest in combination-treated mice. Immunostaining and angiography results showed sparse vascularity in treated xenografts. Endothelial apoptosis was observed only in treated tumors. CONCLUSION: Combination low-dose topotecan and anti-VEGF antibody therapy is antiangiogenic and suppresses tumor growth and metastasis in experimental Wilms tumor more durably than either agent alone.

Effective therapy of a vascular tumor of infancy with vincristine.

Vascular tumors are common in infancy, affecting as many as 10% of children. These lesions often follow a benign course, with an initial proliferative phase followed by spontaneous involution, and require no therapy. Others manifest explosive early growth and Kasabach-Merritt phenomenon, requiring therapeutic intervention. Occasionally, some bulky tumors threaten life or vision because of mass effect, also mandating intervention. Steroids are the mainstay of therapy, but often are ineffective. Interferon alpha (2a and 2b) has been used as second-line therapy in cases of steroid failure. However, interferon therapy has been associated with a significant incidence of spastic diplegia. The authors present the case of a 3-month-old girl in whom respiratory distress secondary to tracheal compression developed. Magnetic resonance imaging and magnetic resonance angiography showed a large cervicothoracic lesion encasing the great vessels and displacing the airway. She did not display associated Kasabach-Merritt phenomenon. The lesion proved refractory to standard steroid therapy, but responded dramatically to 4 cycles of vincristine (0.05 mg/kg). Although this agent has been used in children with life-threatening Kasabach-Merritt phenomenon, this is the first time it has been described in the setting of compromised vital function. Vinca alkaloids recently have been shown to have potent antiangiogenic activities in experimental models. Given the low predicted incidence of side effects at this dose, vincristine used as an antiangiogenic agent may prove an attractive alternative therapy for patients with life-threatening vascular tumors of infancy.

All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and Wilms tumor.

BACKGROUND/PURPOSE: Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction. METHODS: Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals. RESULTS: Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration. CONCLUSIONS: Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.

Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors.

BACKGROUND/PURPOSE: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor. METHODS: VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks. RESULTS: At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%). CONCLUSIONS: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.

Uroepithelium in a colonic diverticulum.

Giant colonic diverticula are rare entities and often present in adulthood as acute diverticulitis. The authors present a case of giant colonic pseudodiverticulum lined with uroepithelium causing bowel obstruction in a neonate. The presence of uroepithelium in a colonic pseudodiverticuium remains unexplained and to the authors' knowledge unreported. This heterotopic tissue may be a result of an embryonic rest or could be urachal in origin adhering initially to the colon and eventually detaching from the umbilicus. These lesions should be resected because of the risk of infection, perforation, or obstruction.

Cloacal exstrophy: a unified management plan.

BACKGROUND/PURPOSE: The belief that patients with cloacal exstrophy have a short and therefore useless colon is all too common. Frequently, the colon is used for urinary or vaginal reconstruction, and the possibility of a pull-through is lost. In the authors' experience, the use of a unified management plan allowed most patients to undergo pull-through and avoid a permanent stoma. METHODS: Twenty-five patients were treated for cloacal exstrophy in the authors' institution from 1985 through 1999. In all patients, bladder closure, omphalocele repair, and creation of a colostomy were performed at birth. All available colon, no matter how small, was incorporated into the fecal stream. After at least 1 year, patients were assessed for the ability to form solid stool through their stoma. Normal colonic length, capacity to form solid stool, or success with a bowel management regimen through the stoma were considered indications for pull-through. Genitourinary reconstruction was contingent on the colorectal plan. RESULTS: Colonic length ranged from normal in 12 patients, 40 to 70 cm in 3 patients, 10 to 30 cm in 4 patients, and less than 10 cm in 2 patients. All 25 patients underwent pull-through. Three are totally continent, 4 are continent with occasional soiling, 11 remain clean with a bowel management regimen, and 4 are too young to assess. One patient was clean, but now refuses bowel management. Two early patients, both with less than 10 cm of colon, now have ileostomies. CONCLUSIONS: During neonatal repair, a colostomy should be formed incorporating all pieces of colon, no matter how small. With time, most patients will be able to form solid stool, and a pull-through should be undertaken if that ability exists. Decisions regarding genitourinary reconstruction should be made only after the gastrointestinal plan is established to achieve the optimal use of available bowel.

The nonoperative management of fistula-in-ano.

BACKGROUND/PURPOSE: Fistulotomy is the accepted treatment for infants with perianal fistula. Although recurrence rates range from 0% to 68%. Based on the experience of a senior colleague who noted that babies suffering from perianal fistula follow a self-limited course the authors decided to determine if this observation was accurate. METHODS: A conservative approach to perianal abscess and fistula was used prospectively in 18 male infants. Abscesses were to be drained only if the baby was very uncomfortable or febrile. Once a fistula developed the authors continued observation until the fistula healed. Data are expressed as mean +/- SD. Mean follow-up period was 37 months. RESULTS: Mean age at onset of symptoms was 4 +/- 3 months. Fistulas developed in 14 patients (77%). All fistulas healed without operation. Four patients had abscesses drained for discomfort (n = 3) or fever (n = 1). No patient required antibiotics. Mean duration of symptoms was 6 +/- 4 months. Four patients in whom fistulas did not form healed after incision (n = 3) or spontaneous drainage (n = 1). All patients currently are asymptomatic. CONCLUSIONS: In healthy neonates, perianal abscess and fistula are self-limited conditions rarely requiring surgical drainage and not requiring antibiotics. The conservative management of perianal abscess and fistula in healthy infants appears to be safe and effective.

Continent appendicostomy in the bowel management of fecally incontinent children.

BACKGROUND: Fecal incontinence is common in children who have anorectal malformations, Hirschsprung's Disease, and spina bifida and can negatively impact their emotional and social development. Enemas have been used as an artificial way to keep children clean and to improve their quality of life. This method is unpleasant for many children, particularly when they reach adolescence. Malone in 1990 described an alternative method in which the appendix is used as a conduit to administer an antegrade enema. METHODS: The authors describe their experience with this new procedure, modified by them, and used in 20 patients. In the original procedure, the base of the appendix is divided, inverted, and reimplanted into the cecum with an antireflux technique. The authors simplify this by plicating the cecum around the appendix to create a one-way valve mechanism but leaving the appendix in its original position. The authors also mobilize the cecum and exteriorize the appendix at the umbilicus to create an inconspicuous stoma. If the native appendix is absent a neoappendix was created from a flap of cecum. RESULTS: Nineteen of 20 patients (95%) are now completely clean 24 hours a day. Stricture of the stoma occurred in two patients and required revision. Leakage at the appendicostomy site occurred in three patients, and two required a tighter plication. CONCLUSIONS: The technique is used to change the route of enema administration, and is only used in patients for whom bowel management with rectal enemas has been proven successful. The appendix must be preserved whenever possible in patients at risk for fecal incontinence.

The effects of "decelerated" rehabilitation following anterior cruciate ligament reconstruction on a hyperelastic female adolescent: a case study.

Current concepts in postoperative anterior cruciate ligament (ACL) reconstruction management include participation in an "accelerated" rehabilitation program. There are no published reports examining the effects of accelerated or conservative rehabilitation on subjects with generalized ligamentous hyperelasticity. The purpose of this case study was to examine the effects of a conservative or "decelerated" rehabilitation program on the functional outcome of a hyperelastic female adolescent athlete following ACL reconstruction. The subject was a 15-year-old female basketball player who sustained a unilateral ACL tear and underwent subsequent ACL reconstruction using a patellar tendon autograft. The subject immediately began participation in a "decelerated" rehabilitation program in which the intensity and rate of progression was decelerated, emphasizing a prolonged period of maximum graft protection. Progress was objectively quantified with a battery of diagnosis-specific tests at scheduled intervals. Results at 52 weeks postoperative revealed normal range of motion, proprioception, balance, knee stability, quadriceps strength, hamstring strength, and subjective assessment values, and only a 4.0% deficit in functional scores. Our results suggest a "decelerated" rehabilitation program may be appropriate for the population with generalized ligamentous hyperelasticity by yielding excellent functional results without compromising the integrity of the graft and, ultimately, knee stability.

Recent advances regarding attention deficit-hyperactivity disorder in adolescence.

This paper reviews recent studies of attention deficit-hyperactivity disorder, focusing on research with implications for adolescents. Only 10 of the 31 recent investigations discussed employed an exclusively adolescent sample, necessitating considerable extrapolation from studies of children or adults or mixed samples with a wide range of ages. Significant advances include increased accuracy of predicting negative outcomes and the identification of adaptive skill dysfunction. Further information has become available on the long-term impact of attention deficit-hyperactivity disorder, and additional data have been reported on risk factors. Other reports have described typical services provided by pediatric and family medicine practices for attention deficit-hyperactivity disorder; beneficial effects of combined behavioral and pharmacologic treatment; absence of adverse effects of methylphenidate on cognitive constriction or tics; and disappointing results for nonstimulant pharmacotherapy. A National Institute of Mental Health multisite treatment study has recently been initiated.

Chronic compartment syndrome caused by aberrant fascia in an aerobic walker.

The following is a case presentation of a 36-yr-old female athlete who presented with the symptoms and signs of chronic anterior compartment syndrome. Pre-exercise and post-exercise tissue pressure measurements revealed increased compartment pressures in both of her anterior leg compartments. Aberrant fascial bands overlying and compressing the anterior compartments were discovered at the time of surgery. Fasciotomies led to complete recovery and return to previous levels of athletic activity. This is the first report of aberrant fascia as a cause of chronic anterior compartment syndrome.

Continuous passive motion after internal fixation of distal humerus fractures.

Two patients with severe intra-articular fractures of the distal humerus were treated with internal fixation and postoperative continuous passive motion (CPM) of the elbow. The CPM machine's range of motion was initially set at 30 degrees to 70 degrees of flexion for one patient and 45 degrees to 90 degrees of flexion for the other. The arc of motion was gradually increased daily without discomfort. There was no occurrence of wound complications, nonunion, loss of reduction, heterotopic ossification, or failure of fixation. At last evaluation, both patients had full pronation and supination. One patient had 0 degrees to 135 degrees of elbow flexion, and the other had 30 degrees to 110 degrees. Both patients had pain-free elbows. CPM was found to be a valuable therapeutic modality in the postoperative management of intra-articular fractures of the elbow.

[Role perception of medical residents in relation to hospital size and specialty].

The resident's perception of the nature of the socialization process during specialization in relation to hospital size and field of specialization was studied. A closed-type questionnaire was administered to 258 residents who in 1984 registered for Phase One of the National Board Examination during their training. The results indicate considerable homogeneity in their perception of the norms and rewards of the practice of medicine. No significant differences were found by field of specialization or size of hospital. However, there were significant differences in the nature of the actual training in relation to the size of the hospital. A great deal of direct training and a large routine workload was reported by residents in medium-sized hospitals as compared with large and small hospitals. Surprisingly, achievements of residents were not congruent with the pattern of training: the highest rate of success in the examination was achieved by residents in large hospitals, a lower rate in small hospitals, while the lowest was in medium-sized hospitals.

Pitfalls in the use of interference screws for anterior cruciate ligament reconstruction: brief report.

Arthroscopically assisted bone patellar tendon bone reconstruction of the anterior cruciate ligament (ACL) is becoming an increasingly popular surgical technique. Use of interference screw fixation of the bone plugs within bony tunnels has been shown to improve fixation and pull-out strength. Several potential pitfalls exist which can jeopardize results of the surgical procedure when this form of fixation is used. This article describes the potential pitfalls and suggests methods to avoid them.

Osteomalacia as a very late manifestation of primary hyperparathyroidism.

An 86-year-old woman with a history of treated hyperthyroidism and a 20-year history of untreated primary hyperparathyroidism developed generalized bone pain and a pseudofracture of the midshaft of the left femur. Laboratory examinations revealed elevated serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels. Serum inorganic phosphate was below normal and 25-hydroxyvitamin D levels were low-normal. An undecalcified transiliac bone biopsy specimen following tetracycline double labeling revealed osteomalacia and osteitis fibrosa. Following treatment with vitamin D and phosphate, the serum inorganic phosphate level rose to normal. There was a decrease in bone pain, and the pseudofracture healed. However, the serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels remained elevated. Longstanding primary hyperparathyroidism causes chronic hypophosphatemia and may lead to osteomalacia. Osteomalacia and its consequences may be part of the spectrum of bone disease seen in patients with longstanding primary hyperparathyroidism.