Inhibition of cyclo-oxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) blockade is an effective therapy for human cancer, yet virtually all neoplasms resume primary tumor growth or metastasize during therapy. Mechanisms of progression have been proposed to include genes that control vascular remodeling and are elicited by hypoperfusion, such as the inducible enzyme cyclooxygenase-2 (COX-2). We have previously shown that COX-2 inhibition by the celecoxib analog SC236 attenuates perivascular stromal cell recruitment and tumor growth. We therefore examined the effect of combined SC236 and VEGF blockade, using the metastasizing orthotopic SKNEP1 model of pediatric cancer. Combined treatment perturbed tumor vessel remodeling and macrophage recruitment, but did not further limit primary tumor growth as compared to VEGF blockade alone. However, combining SC236 and VEGF inhibition significantly reduced the incidence of lung metastasis, suggesting a distinct effect on prometastatic mechanisms. We found that SC236 limited tumor cell viability and migration in vitro, with effects enhanced by hypoxia, but did not change tumor proliferation or matrix metalloproteinase expression in vivo. Gene set expression analysis (GSEA) indicated that the addition of SC236 to VEGF inhibition significantly reduced expression of gene sets linked to macrophage mobilization. Perivascular recruitment of macrophages induced by VEGF blockade was disrupted in tumors treated with combined VEGF- and COX-2-inhibition. Collectively, these findings suggest that during VEGF blockade COX-2 may restrict metastasis by limiting both prometastatic behaviors in individual tumor cells and mobilization of macrophages to the tumor vasculature.

Vascular characterization of clear cell sarcoma of the kidney in a child: a case report and review.

Clear cell sarcoma of the kidney (CCSK) is uncommon pediatric renal tumor and can present a significant therapeutic challenge in those patients whose tumors spread beyond the kidney. Thus, identifying potential novel targets for treatment may be clinically important. Clear cell sarcoma of the kidney is characterized by a unique vascular pattern, in which nests of tumor cells are separated by regularly-spaced, fine fibrovascular septa. This distinctive histopathology raises the possibility that understanding the factors which drive angiogenesis in CCSK tumors may suggest new therapeutic targets. Here, we describe a case of CCSK and present immunohistochemical studies of its vasculature.

Gastric tube-pericardial fistula: a remote complication of esophageal replacement for long gap esophageal atresia.

Several short and long-term complications of esophageal replacement have been described in the literature. We report the case of a gastric tube-pericardial fistula occurring 20 years after initial repair of long gap esophageal atresia with a reversed gastric tube.

Multivariate model for predicting recurrence in congenital diaphragmatic hernia.

PURPOSE: Risk factors that predispose children with congenital diaphragmatic hernia (CDH) to recurrence remain poorly defined. We report a large series of recurrent CDH and ask whether prenatal patient factors or postnatal treatment variables better predict recurrence. METHODS: Two hundred thirty-eight neonates with unilateral CDH underwent repair from 1990 to 2006. Data were assessed by chi(2) and Mann-Whitney U tests. Multivariate regression identified independent predictors of recurrence. Statistical significance was set at P < .05. RESULTS: We identified 24 recurrences (10%). Median time from repair to recurrence diagnosis was 4.9 months. Patients with recurrence were older (P = .02) and more often required abdominal wall patches at initial repair (P = .01) compared to nonrecurrence patients. Postoperative length of stay (LOS) after initial repair (P < .01) and morbidity (P = .01) were greater in recurrence patients. Use of diaphragm patch at initial repair was greater in patients with recurrence but only approached statistical significance (P = .05). Only 2 variables independently predicted recurrence by multivariate regression as follows: abdominal (not diaphragm) wall patch during initial repair (odds ratio [OR] 3.50; P = .04) and postoperative LOS (OR, 1.012; P = .01). CONCLUSION: Neonates at risk for CDH recurrence are better identified by postnatal treatment variables than by prenatal patient factors. Although age at repair and diaphragm patch use are greater in recurrence patients, the only factors to independently predict recurrence were postoperative LOS and abdominal wall patch use. These data can help optimize follow-up regimens.

Percutaneous distal perfusion of the lower extremity after femoral cannulation for venoarterial extracorporeal membrane oxygenation in a small child.

Femoral cannulation in pediatric patients requiring extracorporeal membrane oxygenation (ECMO) is commonly associated with distal limb ischemia. Authors have previously reported successful lower limb perfusion using various open techniques to cannulate a distal lower extremity artery at the time of initial ECMO cannulation. These procedures include open femoral artery antegrade cannulation and distal posterior tibial artery retrograde cannulation in older children and adults. Such approaches require ample vessel diameters to accommodate an arteriotomy and catheter insertion and, therefore, are of limited use in smaller children. We hypothesized that after femoral artery cannulation for ECMO, a percutaneous technique of distal limb perfusion might offer unique advantages when treating lower extremity ischemia in small pediatric patients. We report a technique for percutaneous antegrade cannulation in a 4-year-old patient shortly after her primary cannulation for venoarterial ECMO via the femoral artery.

Polyorchidism in a child with imperforate anus.

Polyorchidism is a rare diagnosis. When recovered, it is frequently found in combination with other urologic pathologies. We report the case of a 14-month-old child with imperforate anus who was found to have polyorchia during repair of his inguinal hernia. Although cryptorchidism is not an uncommon finding in patients with imperforate anus, polyorchidism has never been reported. This is an unusual presentation of a rare entity.