Suramin analogs inhibit human angiogenesis in vitro.

BACKGROUND: Suramin is a polysulfonated naphthylurea that inhibits tumor cell proliferation and angiogenesis, but the widespread use of this drug has been limited by significant neurologic toxicity. A series of suramin analogs that may exhibit less toxicity in vivo have been synthesized. We hypothesized that these novel analogs would have antiangiogenic properties equal to or greater than those of suramin when evaluated in an in vitro human placental vein angiogenesis model. METHODS: Human placental veins (n = 72 per group) were cultured in a 0.3% fibrin clot for a period of 14 days. Three suramin analogs (NF 145, NF 248, NF 293) and suramin were tested at 56 and 560 microM concentrations to determine their effect on the development of an angiogenic response. Experiments were repeated for each analog on veins from three different placentas. The percentage of wells that initiated an angiogenic response was calculated and compared with initiation in a control group (n = 141). RESULTS: The three suramin analogs inhibited angiogenesis in a dose-dependent fashion, with all compounds exhibiting near-complete inhibition of angiogenesis at 560 microM. The effects of these analogs were equal to or greater than those of suramin. CONCLUSION: Suramin analogs with structural alterations inhibit human angiogenesis at concentrations equivalent to those seen in vivo. These analogs may be more effective antiangiogenic agents than suramin and may have less potential for toxicity.

Laparoscopic fundoplication in children with previous abdominal surgery.

BACKGROUND/PURPOSE: In our institution, many children requiring antireflux surgery for gastroesophageal reflux have had previous abdominal surgery, usually gastrostomy tube or ventriculoperitoneal (VP) shunt placement. The authors review their laparoscopic Nissen fundoplication (LNF) experience in children with previous abdominal surgery assessing surgical outcome. METHODS: A total of 82 consecutive LNFs performed at our institution between January 1996 and September 1998 were reviewed. Follow-up ranged from 1 month to 32 months (average, 8.9 months). LNF was performed without dividing short gastric vessels (Rosetti modification) through a standard 5-port technique. RESULTS: A total of 26 of 82 patients (31.7%) had previous abdominal surgery and were divided into 2 groups: gastrostomy (n = 17) and VP shunt (n = 11) with 2 crossovers. A total of 14 of 17 (82.3%) in the gastrostomy group had percutaneous endoscopic gastrostomy (PEG) placement versus 3 of 17 (17.6%) by open technique (open). Four patients in the VP group had multiple surgeries (range, 1 to 10, average, 2.3). LNF was completed in 25 of 26 (96.2%). One operation was converted to an open procedure because of severe adhesions. In 13 of 17 (76.5%) the previous gastrostomy was not taken down. In 4 of 17 (23.5%), the gastrostomy was taken down to complete the procedure: 2 of 3 (66.7%) of the open group versus 2 of 14 (14.3%) of the PEG group. All 11 (100%) of the VP group had successful LNF. Two of 11 (18.2%) had shunt dysfunction at 2 months (shunt infection) and 4 months (clogged distal shunt), respectively. There have been no cases of recurrent reflux, and all gastrostomies and VP shunts were functional at the time of this report. CONCLUSIONS: Previous abdominal surgery is common in children with gastroesophageal reflux disease requiring an antireflux procedure. The authors conclude from these preliminary results that laparoscopic Nissen fundoplication can be performed safely with minimal morbidity and excellent functional results in children with gastrostomies or ventriculoperitoneal shunts.