Denis A. Cozzi

Clinical Significance of CXC Chemokine Receptor-4 and c-Met in Childhood Rhabdomyosarcoma

Purpose: The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1 and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in ≥5% of tumor cells from 40 of 40 tumors, with 14 of 40 cases showing ≥50% of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P = 0.006), unfavorable primary site (P = 0.009), advanced group (P < 0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P < 0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n = 16), a significant enrichment in the percentage of CXCR4-positive (P = 0.001) and c-Met–positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.

The effect of glossopexy on weight velocity in infants with Pierre Robin syndrome

AIM In infants with Pierre Robin syndrome (PRS), mandibular distraction may be more advantageous than glossopexy as it not only relieves oropharyngeal airway obstruction but also reverses body growth retardation. Because no data are available on body weight velocity after glossopexy, we assessed longitudinally the body weight velocity in a cohort of children undergoing glossopexy. METHODS The records of 48 infants with PRS undergoing glossopexy after unsuccessful nonoperative treatment between 1981 and 2005 were reviewed. Weight measurements were analyzed at 4 time-points: at birth, on admission for glossopexy, on admission for lysis of lip-tongue adhesion (TLA), and at follow-up. Weight velocity was assessed using Tanners tables. MAIN RESULTS Adhesion dehiscence occurred in 9 patients (18.7%). Lip-tongue adhesion resolved airway compromise in 36 infants (75%). Release of TLA was accomplished in 34 patients. Data on weight velocity from birth to follow-up (mean, 5.57 +/- 0.59 years) were available for 31 patients. After glossopexy, mean body weight increased from the 9.7 +/- 2.6th to the 17.5 +/- 4.6th percentile (P > .05), whereas mean weight velocity increased from the 19.1 +/- 4.9th to the 74.2 +/- 4.7th percentile (P < .001). No temporal correlation was found between glossopexy and oropharyngeal dysphagia. CONCLUSION In infants with PRS, glossopexy is a valid alternative to mandibular distraction because it does not cause decline in body growth.

Pattern of cardiovascular anomalies associated with esophageal atresia: support for a caudal pharyngeal arch neurocristopathy.

Patients with cephalic neurocristopathy (an abnormality of neural crest differentiation) present a striking pattern of associated cardiovascular anomalies (CVA). Therefore, to support the hypothesis that esophageal atresia (EA) may be related to a defective contribution from the cephalic neural crest, we studied the pattern of CVA associated with EA. Medical records of 99 patients with isolated EA, 101 with isolated anorectal malformations (ARM) and 15 with both EA and ARM, consecutively admitted to our unit, were reviewed. The prevalence and pattern of CVA associated with isolated EA or isolated ARM were compared on the assumption that the cranial or caudal location of a major malformation is related to a different regional patterning of associated anomalies. The prevalence of CVA was 39% in patients with isolated EA and 7% in those with isolated ARM (p < 0.01). Neural crest–related CVA (aortic arch anomalies, conotruncal defects, and superior vena cava malformations) accounted for 72% of all CVA in patients with isolated EA versus 14% in those with isolated ARM (p < 0.02). In patients with isolated EA, anomalies of the fourth and sixth aortic arch derivatives accounted for 75% of all neural crest related CVA. The present pattern of CVA in infants with EA supports the concept that EA may be related to an abnormal contribution from caudal portion of cephalic neural crest.

Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study.

Mild‐to‐moderate renal function loss may be an independent risk factor for cardiovascular disease and overall mortality. As in adults with renal carcinoma nephrectomy is associated with an high risk for moderate renal function loss, we aimed to assess the renal function adaptation over a long period of time in children with unilateral renal tumor (URT).

Pneumatic balloon dilation in pediatric achalasia: efficacy and factors predicting outcome at a single tertiary pediatric gastroenterology center

BACKGROUND The use of pneumatic dilation (PD) is well established in adults with achalasia; however, it is less commonly used in children. OBJECTIVE To evaluate the efficacy of PD in pediatric achalasia and to define predictive factors for its treatment failure. DESIGN Single-center, prospective cohort study. SETTING Academic tertiary referral center. PATIENTS Twenty-four patients with achalasia were enrolled from January 2004 to November 2009 and were followed for a median of 6 years. INTERVENTION PD was performed with the patients under general anesthesia. MAIN OUTCOME MEASUREMENTS Efficacy and safety of PD. Follow-up was performed by using the Eckardt score, barium swallow contrast studies, and esophageal manometry at baseline; 1, 3, and 6 months after dilation; and every year thereafter. A Cox regression model was used to identify independent predictors of failure after the first PD. RESULTS The PD success rate was 67%. In 8 patients, the first PD failed, but the parents of one patient refused a second PD and requested surgery. Of the 7 patients who underwent repeated treatment, the second PD failed in 3 (43%). Overall, only 3 of the 24 patients underwent surgery (overall success rate after a maximum of 3 PDs was 87%). Multivariate analysis showed that only older age was independently associated with a higher probability of the procedure success (hazard ratio [HR] 0.66; 95% CI, 0.45-0.97). LIMITATIONS Small sample size, single-center study. CONCLUSIONS PD is a safe and effective technique in the management of pediatric achalasia. Young age is an independent negative predictive factor for successful clinical outcome.

Infantile Abdominoscrotal Hydrocele: A Not So Benign Condition

PURPOSE Infantile abdominoscrotal hydrocele is a rarely described condition. We report the outcome of the largest single institution experience managing these lesions. MATERIALS AND METHODS We retrospectively reviewed descriptive case series of all infants treated between January 1998 and December 2007. Postoperative followup ranged from 3 to 107 months (median 48). RESULTS A total of 18 consecutive patients underwent abdominoscrotal hydrocele repair at age 3 to 21 months (median 8). The first 13 patients underwent inguinal hydrocelectomy, which consisted of high ligation of the processus vaginalis and complete excision of the abdominal component of the lesion. The remaining 5 patients underwent plication of the tunica vaginalis accomplished through the scrotum. Included in this group were 2 patients initially treated expectantly because the lesion was without undue tension at diagnosis. Both cases demonstrated spontaneous resolution of the abdominal component of the lesion but ultimately required surgery for scrotal hydrocele. Overall 23 testes (5 bilateral lesions) were operated on, of which 18 had some degree of testicular dysmorphism detected by ultrasonography or during surgery and 15 fully recovered postoperatively. A total of 11 patients experienced 1 or more postoperative complications, including persistent scrotal swelling (7), hypoplastic testis (3), scrotal hematoma (2), inguinal hernia (1) and cryptorchidism (1). Morbidity related to scrotal hydrocelectomy was negligible. There were no recurrences of abdominoscrotal hydrocele in the series. CONCLUSIONS Tense infantile abdominoscrotal hydroceles are associated with a high rate of testicular dysmorphism, which is often reversed by early intervention. Simple transscrotal plication of the tunica vaginalis represents an effective procedure with decreased postoperative complications.

Radial artery pseudoaneurysm successfully treated by compression bandage

In children, surgery for radial artery pseudoaneurysm (PA) may be followed by growth retardation of the hand because of inadequate blood flow. We believe this is the first report of a child with PA of the radial artery cured by compression bandage. Conservative management is a safe and valuable initial treatment option for uncomplicated radial PA.

In Reply: Enucleative Surgery for Stage I Nephroblastoma with a Normal Contralateral Kidney

PURPOSE Tumor enucleation is not recommended for children with nephroblastoma and a normal contralateral kidney. However, in adults with unilateral low stage renal cell carcinoma tumor enucleation may offer an alternative to radical nephrectomy, since functioning renal tissue is preserved without a greater risk of residual microscopic disease. Enucleative surgery may be more reasonable in children with nephroblastoma, because the risk of relapse can be reduced with chemotherapy. Therefore, we prospectively evaluated the feasibility of enucleative surgery in children with stage I unilateral nephroblastoma. MATERIALS AND METHODS Between 1992 and 1995, 13 children with nephroblastoma and a normal contralateral kidney were consecutively admitted to our surgical unit. Possible candidates for tumor enucleation were evaluated according to certain criteria, including stage I disease at diagnosis, well-defined margins on post-contrast computerized tomography and at least 50% of the functioning kidney could be preserved. Preoperative and postoperative chemotherapy was given in all cases. RESULTS Of 4 children with preservation of more than 50% of the functioning kidney 3 were considered eligible for enucleation. The tumors, which were confined to the mid kidney in 2 children and upper renal pole in 1, were successfully enucleated without hypothermia or vascular occlusion. All 3 children are disease-free at 49, 48 and 26 months of followup, respectively. Renal function has been almost completely restored postoperatively. CONCLUSIONS These preliminary data suggest that enucleative surgery may be a reasonable option in select children with stage I nephroblastoma and a normal contralateral kidney.

Chronic Kidney Disease in Children With Unilateral Renal Tumor

PURPOSE In patients who have undergone nephrectomy lower stage chronic kidney disease may develop, which is an independent risk factor for cardiovascular disease and overall mortality. We investigated whether the prevalence of lower stage chronic kidney disease is related to the amount of renal parenchyma excised in children with unilateral renal tumor. MATERIALS AND METHODS A total of 15 patients treated with nephrectomy and 10 treated with nephron sparing surgery were enrolled at a single academic center. The Kidney Disease Outcomes Quality Initiative guidelines were used to classify patients by chronic kidney disease stage based on estimated glomerular filtration rate values. The Modification of Diet in Renal Disease study equation and Schwartz equation were used in patients older and younger than 17 years, respectively. RESULTS At a mean followup of more than 12 years 8 patients who had undergone nephrectomy and 1 treated with bilateral nephron sparing surgery presented with stage II chronic kidney disease (estimated glomerular filtration rate 60 to 89 ml/min/1.73 m(2)). Sequential measurements from diagnosis to 12 to 17 years postoperatively showed that stage II chronic kidney disease in patients who had undergone nephrectomy manifested as a negligible postoperative increase in mean ± SD estimated glomerular filtration rate (75.7 ± 25.5 vs 79.4 ± 3.9 ml/min/1.73 m(2), p = 0.6). Five of the 8 patients presented with stage II chronic kidney disease even before nephrectomy. The other 7 patients who had undergone nephrectomy and those treated with nephron sparing surgery presented with a significant postoperative increase in mean ± SD estimated glomerular filtration rate (81.1 ± 24 vs 102.3 ± 3 ml/min/1.73 m(2), p = 0.02, and 88.7 ± 2 vs 107.4 ± 14 ml/min/1.73 m(2), p = 0.005, respectively). CONCLUSIONS A subset of children with unilateral renal tumor presents before and/or after nephrectomy, and not after nephron sparing surgery, with stage II chronic kidney disease, probably due to a reduced renal reserve capacity. Whether patients with preoperative renal dysfunction may benefit from nephron sparing surgery should be studied in a cooperative clinical trial setting.

Adenomyomatosis of the Gallbladder in Childhood: Report of a Case and Review of the Literature

ABSTRACTAdenomyomatosis of the gallbladder is considered an acquired pathologic condition that affects adults, with only 2 cases previously described in childhood. We report on a 5-year-old boy with incidental detection of this lesion by ultrasonography. Pathologic and clinical assessments are discussed in addition to treatment decision-making, including current insights into the relation between adenomyomatosis and malignancy of the gallbladder. The liberal use of ultrasonography in children with abdominal pain may result in detection of an increasing number of asymptomatic patients. Caregivers should be aware of this condition and its therapeutic implications in the pediatric population.