Keith A. Thatch

A comparison of laparoscopic and open Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit population

INTRODUCTION The aim of this study was to compare outcomes after laparoscopic and open techniques for Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit (NICU) population. METHODS The medical records for NICU inpatients who underwent laparoscopic and open Nissen fundoplication and gastrostomy placement from August 2002 to August 2008 were reviewed after Institutional Review Board approval. Each technique was compared with regard to operative time, estimated blood loss, postoperative 24-hour narcotic requirements, time to goal feeds, and complication rates. Analysis of variance was used to determine statistical significance. Data are quoted as mean +/- SEM. RESULTS Fifty-seven NICU patients underwent fundoplication and gastrostomy placement (25 laparoscopic and 32 open). The time to goal feeds was significantly shorter for the laparoscopic group (4.3 +/- 0.4 vs 6.1 +/- 0.6 days, P = .04). The 24-hour postoperative narcotic requirement was significantly lower in the laparoscopic group (0.24 +/- 0.05 vs 0.55 +/- 0.08 mg/kg, P = .007). Operation times (111 +/- 5 [open] vs 113 +/- 5 minutes, P = .76) and estimated blood loss (13 +/- 2 [open] vs 11 +/- 1 mL, P = .33) were comparable for both groups. CONCLUSION Laparoscopic and open techniques for Nissen fundoplication with gastrostomy placement are safe and appropriate treatment methods with equivalent operating times for the treatment of gastroesophageal reflux in the NICU population.

Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease

BACKGROUND/PURPOSE The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model. METHODS Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (alpha-naphthylisothiocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 mug/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 mug/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)-6 and tumor necrosis factor alpha expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days. RESULTS Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor alpha expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups. CONCLUSION Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.

Growth Factor Manipulation of Intestinal Angiogenesis: A Possible New Paradigm in the Management of Inflammatory Bowel Disease

BACKGROUND Using the transgenic HLA-B27 rat model of inflammatory bowel disease (IBD), we have previously demonstrated hepatocyte growth factors (HGF) potential to ameliorate diarrhea and decrease bowel injury. This study was designed to assess the effect of HGF on the neovascularization and inflammation in IBD. MATERIALS AND METHODS Female transgenic HLA-B27 rats were divided into two groups: group 1, saline (control, n = 6); group 2, HGF (150 mug/kg/d, n = 9). Treatments were delivered into the jugular vein via a 14-d subcutaneously placed osmotic mini-pump. Intestinal microvascular density (MVD), histologic inflammatory score, inflammatory cell infiltration, and cytokine expression (tumor necrosis factor-alpha {TNF-alpha}, interferon-gamma {IFN-gamma}, and interleuken-2 {IL-2}) were assessed. Analysis of variance (ANOVA) was used to determine statistical significance. RESULTS Administration of HGF resulted in variable but significant alterations in ileal and colonic histology compared with control animals. Compared with group 1, inflammatory cell infiltration was significantly reduced in group 2 (7.7 +/- 1.2 versus 13.3 +/- 2.1 SEM, P < 0.05). Enzyme linked immunosorbent assays (ELISA) demonstrated significantly less expression of ileal IFN-gamma, ileal IL-2 and colonic IL-2 in group 2 (P < 0.05) (Fig. 1). Of importance is that Group 2 exhibited significantly greater MVD in the ileum and colon, both P < 0.05 (Figs. 2 and 3). CONCLUSION HGF stimulates neovascularization while modulating the intestinal inflammatory response. This is the first demonstration in which a growth factor (HGF) stimulates nonpathologic angiogenesis in an animal model of IBD. HGF administration may be beneficial in the clinical management of IBD.

Hepatocyte growth factor and omega-3–enriched feeds have a synergistic effect on mucosal mass in an animal model of inflammatory bowel disease

BACKGROUND Hepatocyte growth factor (HGF) decreases intestinal inflammation and cytokine levels in an animal model of inflammatory bowel disease (IBD). Luminal omega-3 (OM-3) is anti-angiogenic, reduces inflammation, and may decrease symptoms in patients with Crohns disease. This study evaluates the synergism of HGF and OM-3. METHODS Twenty adult female transgenic HLA-B27 rats were divided into 4 groups: group 1: regular feeds, IV saline; group 2: OM-3-enriched feeds, IV saline; group 3: regular feeds, IV HGF (150 µg/kg per day); and group 4: OM-3-enriched feeds, IV HGF(150 µg/kg per day). Rats were killed at 14 days after pump placement. Small and large bowel mucosa was harvested, and DNA and protein were extracted and quantified. Statistical analysis was done by analysis of variance with post-hoc Tukeys HSD test. RESULTS Content of protein and DNA in the ileum were significantly increased by supplementation of HGF (P < .001, P < .01, respectively) alone. OM-3 significantly increased protein content but not DNA (P = .02, P = 0.3, respectively). Combined, they had a synergistic effect greater than either supplement alone (P = .0001, P = .002, respectively). In the colon, HGF and OM-3 did not significantly increase protein or DNA content individually or together. CONCLUSIONS This is the first demonstration of the synergistic effect of a growth factor (HGF) and a dietary supplement (OM-3) in an immunologic model of IBD.

Gene alterations and intestinal mucosal changes following growth factor and omega-3 exposure in a rat model of inflammatory bowel disease

BACKGROUND We have previously shown that there is synergism between Hepatocyte Growth Factor (HGF) and Omega-3 (OM-3) enriched feeds using an immunologic model of inflammatory bowel disease (IBD). This combination decreased inflammation and cytokine levels and increased microvascular density and mucosal mass. This study evaluates the gene alterations that occurred using this same model. METHODS Twenty adult female transgenic HLA-B27 rats were divided into four groups: Group 1: (Regular feeds, IV saline); Group 2: (OM-3 feeds, IV saline); Group 3: (Regular feeds, IV HGF 150 μg/kg/day); Group 4: (OM-3 feeds, IV HGF 150 μg/kg/day). Rats were sacrificed 14 days after pump placement. Bowel was harvested and RNA extracted. Microarray gene chips were used. Statistical analysis was done by analysis of variance using Partek Genomics Suite. Results were significant if fold change was more than 2 or less than -2, with P<0.05. RESULTS In the ileum, HGF up- or down-regulated 34 genes, while OM-3 affected 60 genes. Together 68 genes were affected. Families with a synergistic effect included Solute Carrier Proteins, ATP Binding Cassette Proteins, and Matrix Metalloproteinases. In the colon, 23 genes were affected by HGF, while 66 genes were affected with OM-3. Combined exposure affected 32 genes, including a synergistic effect on solute carrier proteins, aquaporins, and immunologic factors. CONCLUSIONS There is a synergistic gene alteration effect of exposure of two (HGF and Omega-3 enriched feeds) agents on bowel mucosa. Of most interest was the synergistic effect on the solute carrier protein family, a previously identified gene family up-regulated in response to intestinal failure.