Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 h into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum were assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of critical progenitor/stem cell and Paneth cell populations in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared with NEC littermates. Further, the intestinal stem cell and crypt niche that include Paneth cells, SOX9+ cells, and LGR5+ stem cells were restored with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage.NEW & NOTEWORTHY These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.

Is OM-3 synergistic with GLP-2 in intestinal failure?

INTRODUCTION: Glucagon-like peptide-2 (GLP-2) is a known intestinal growth factor that enhances mucosal mass and function in residual small intestine after massive small bowel resection (MSBR). Luminal omega-3 (OM-3) has been shown to have some growth factor properties. It is possible that their mechanisms of action differ. Thus, we hypothesized that administering these two substances together may have a synergistic effect. METHODS: A total of 60 adult female Sprague-Dawley rats underwent 80% MSBR and divided as follows (n = 15/group): Saline (Control) + regular feeds; GLP-2 + regular feeds; Saline + OM-3 enriched feeds; and GLP-2 + OM-3 enriched feeds. Five animals per group were sacrificed at 7, 14, and 28 days. Small intestine mucosa was harvested. DNA and protein content were measured (mucosal mass markers) at all three time points. Galactose and Glycine absorption were measured (functional capacity markers) at 28 days. Statistical analysis was done by ANOVA with post hoc Tukey's HSD test. RESULTS: At all three time points, DNA was increased in all treatment groups compared to control (P < 0.05), but GLP-2 + OM-3 group did not have increased DNA content when compared to either treatments alone. At 7 and 14 d, all three treatment groups had increased protein content compared to control (P < 0.05). At 28 d, GLP-2 + OM-3 did not have increased protein content compared to control or individual treatments (P < 1.0). All three treatment groups had increased absorption of galactose and glycine compared to control (P < 0.05) but not each other. CONCLUSIONS: Individually, GLP-2 and OM-3 are very effective in enhancing the adaptive process by increasing mucosal mass and function, at all three time points. More importantly, clinically, GLP-2 and OM-3 increase substrate absorption in a rat model of intestinal failure. However, the combination is not synergistic.

Successful endovascular repair of exsanguinating penetrating carotid artery injury in two pediatric patients.

Immediate operative exploration has been considered mandatory for all penetrating injuries to Zone II of the neck and in any patient who is unstable, regardless of the location of the injury. We report two cases of penetrating carotid artery injuries in children successfully managed with endovascularly placed covered stents. These cases demonstrate that endovascular carotid artery repair can be considered in children, including in patients with Zone II injuries and in initially unstable patients.

Position statement on fetal myelomeningocele repair.

Following the promising multicenter randomized trial results of in utero fetal myelomeningocele repair; we anticipate that an increasing number of tertiary care centers may want to offer this therapy. It is essential to establish minimum criteria for centers providing open fetal myelomeningocele repair to ensure optimal maternal and fetal/pediatric outcomes, as well as patient safety both short- and long-term; and to advance our knowledge of the role and benefit of fetal surgery in the management of fetal myelomeningocele. The fetal myelomeningocele Maternal-Fetal Management Task Force was initially convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to discuss the implementation of maternal fetal surgery for myelomeningocele. The decision was made to develop the optimal practice criteria presented in this document for the purpose of medical and surgical leadership. These criteria are not intended to be used for legal or regulatory purposes.

Novel therapies for the management of short bowel syndrome in children.

Short bowel syndrome (SBS) is the most common cause of intestinal failure in children. It is defined as the inability to maintain adequate nutrition enterally as a result of a major loss of the small intestine. SBS is a life-threatening entity associated with potential significant morbidity and mortality. The etiology in the pediatric age group includes necrotizing enterocolitis (32%), atresia (20%), volvulus (18%), gastroschisis (17%), and aganglionosis (6%). It is characterized by substrate malabsorption, electrolyte imbalance, intestinal bacterial overgrowth, steatorrhea, and weight loss. Current medical management includes parenteral nutrition, progressive feeds as tolerated, various medications, and surgical manipulations. However, frequently this management is not successful in achieving the goal of attaining normal growth and development without parenteral nutrition. It has been known for decades that there is a normal physiologic response of the residual intestine to massive bowel resection referred to as intestinal adaptation. The mechanisms that control this process are unknown. Unfortunately, intestinal adaptation and the current management are not always successful. As a result of new knowledge regarding the pathophysiology of SBS over the past two decades, several novel strategies have been developed in experimental animal models as well as limited clinical trials in infants and children. They can be divided into several categories that potentially influence intestinal (1) absorption, (2) secretion, (3) motility, and (4) adaptation. More recently, newer modalities have been studied including small intestine transplantation, and the use of specific intestinal growth factors. Ultimately, tissue and organ engineering will become the treatment for infants and children with SBS.

Intralobar pulmonary sequestration: an uncommon case with triple arterial supply and systemic venous drainage.

Pulmonary sequestration is a rare congenital pulmonary malformation. We report a case of a 10-month-old infant with intralobar pulmonary sequestration diagnosed in utero. The lesion had an uncommon blood supply consisting of three large arteries deriving from the thoracic aorta and venous drainage into the inferior vena cava.

Chronology of the effect of massive small bowel resection and hepatocyte growth factor (HGF) on intestinal adaptation.

BACKGROUND: We previously demonstrated that hepatocyte growth factor (HGF) increases mucosal protein and DNA content at single time points during intestinal adaptation in rats. This study evaluates mucosal changes after massive small bowel resection (MSBR) and with the addition of IV HGF measured over the timeframe of intestinal adaptation. METHODS: Sixty adult female Sprague-Dawley rats were divided into three groups and underwent massive small bowel resection (MSBR), MSBR+HGF (intravenous 150 mg/kg/d), or sham operation (control). Five animals per group were sacrificed at 7, 14, 21, and 28 d. Ileal mucosa was harvested and DNA and protein extracted. DNA content (ug/mg mucosa) was measured at 260 nm and protein content (ug/mg mucosa) was measured using the Bradford assay. MIB-5 immunohistochemical staining was done to confirm that the increased DNA content was due to proliferation. Statistical analysis was by ANOVA with post-hoc Tukey's HSD test. RESULTS: At 7 and 14 d, protein concentration was increased following HGF administration in comparison to MSBR alone and in control rats (P<0.05 and P<0.03, respectively). Mucosal DNA content in the MSBR-HGF rats was significantly increased over MSBR and control groups at 21 and 28 d (P<0.02 and P<0.004, respectively). MIB-5 immunohistochemical staining correlated with mucosal DNA content at 21 and 28 d (P<0.0005 and P<0.002, respectively). CONCLUSIONS: The mucosal response to MSBR for the period 7-14 d after surgery demonstrates that protein content is increased due to an emphasis on hypertrophy, whereas at 21-28 d hyperplasia is the primary change as demonstrated by the increase in DNA content. This response was enhanced by HGF. This is the first demonstration correlating the bimodal gene response during intestinal adaptation to the bimodal mucosal response. Also, this is the first demonstration of a biphasic response by the mucosa to HGF during intestinal adaptation.

Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury.

BACKGROUND: Total parenteral nutrition (TPN) induced liver failure is the leading indication for transplantation in children. Our previous research demonstrated the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in the amelioration of TPN-induced liver injury. This study was designed to ascertain the optimum concentration of HGF in an animal model of TPN-induced liver injury. MATERIALS AND METHODS: Twenty adult female Sprague-Dawley rats underwent 70% small bowel resection and placement of venous catheters connected to subcutaneous osmotic minipumps. Four groups (n=5 each) based on the contents of the osmotic pump were utilized as follows: group 1 (control): saline; group 2: HGF 75 mcg/kg/d; group 3: HGF 150 mcg/kg/d; and group 4: HGF 250 mcg/kg/d. Each rat received 14 d of TPN without enteral nutrition. After sacrifice, the liver was harvested. Hepatic inflammation was evaluated using antibodies for TNF-α and IL-6. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique. RESULTS: All concentrations induced statistically significantly less IL-6 and TNF- α expression compared to the control animals. Increased efficacy was demonstrated with increasing dose concentration up to 150 mcg/kg/d but not 250 mcg/kg/d. Apoptotic activity was decreased statistically significantly for all dose concentrations compared with the controls, as well as to increases in dose concentration. CONCLUSIONS: Increasing concentrations of HGF were directly correlated with increased modulation of inflammatory response and apoptotic index in this animal model for TPN-induced liver injury, up to 150 mcg/kg/d. Further increases were significant with respect to apoptotic index only. Further investigations are warranted to determine if HGF may be useful to minimize TPN-induced liver injury in children.

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 factor's (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.

A molecular biomarker for prediction of clinical outcome in children with ASD, constipation, and intestinal inflammation.

In children with autism spectrum disorder (ASD) who present to the gastroenterologist with chronic constipation on a background of colonic inflammation, we have identified two distinct clinical subtypes: (1) patients who experience a sustained state of GI symptomatic remission while on maintenance anti-inflammatory therapy (fast responders) and, (2) those with recurrent right-sided fecal loading requiring regular colon cleanouts during treatment for enterocolitis (slow responders). We hypothesized that a detailed molecular analysis of tissue from the affected region of the colon would provide mechanistic insights regarding the fast versus slow response to anti-inflammatory therapy. To test this, ascending colon biopsy tissues from 35 children with ASD (20 slow responders and 15 fast responders) were analyzed by RNAseq. Hierarchical cluster analysis was performed to assign samples to clusters and gene expression analysis was performed to identify differentially expressed transcripts (DETs) between samples within the clusters. Significant differences were found between the two clusters with fast responder-predominant cluster showing an upregulation of transcripts involved in the activation of immune and inflammatory response and the slow responder-predominant cluster showing significant over-representation of pathways impacting colonic motility (e.g. genes involved in tryptophan and serotonin degradation and mitochondrial dysfunction). Regression analysis identified a single long non-coding RNA that could predict cluster assignment with a high specificity (0.88), sensitivity (0.89) and accuracy (0.89). Comparison of gene expression profiles in the ascending colon from a subset of patients with ASD, chronic right-sided fecal loading constipation and a slow versus fast response to therapy has identified molecular mechanisms that likely contribute to this differential response following the primary therapeutic intervention (i.e. treatment for colonic inflammation with brief induction immunosuppression followed by maintenance non-steroidal anti-inflammatory therapy). Importantly, we have identified a transcript that, if validated, may provide a biomarker that can predict from the outset which patients will be slow responders who would benefit from an alternate therapeutic strategy in treating their constipation.

Development of a Reproducible Model of Parenteral Nutrition-Associated Liver Disease in Rats.

PURPOSE: For patients with intestinal failure, parenteral nutrition (PN) is a life-saving therapy. Unfortunately, hepatic dysfunction will occur in 40 to 60% of children on long-term PN. While the hepatic dysfunction is likely multifactorial, one important chemical component of the disease may be aluminum contamination of the PN. Previous studies have shown a reduction in liver injury by decreasing the aluminum concentration in PN in a pig model. We sought to develop a rat model of PN-associated liver disease (PNALD) with parenteral aluminum. METHODS: Adult Sprague-Dawley rats had intravenous long-term catheters placed. The control group underwent daily injections of saline. The study rats had daily injections of either 2 or 3 mg/kg aluminum chloride (AlCl3). At the end of 4 weeks, the rats were euthanized and liver and blood samples were taken. The livers were analyzed and graded by a pathologist for histological evidence of liver degeneration and acute and chronic inflammation. The serum was analyzed for total bilirubin, alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). RESULTS: There was no difference in serum values of total bilirubin, alkaline phosphatase, ALT, or AST. There was no difference in acute inflammation among the groups (1 [control], 1.2 [2 mg/kg], 1.1 [3 mg/kg]). The rats treated with parenteral aluminum had significantly more Kupffer cells than the control group (0.1 [control], 3 [2 mg/kg], 2.2 [3 mg/kg], p < 0.0001 [control vs. 2 mg/kg] and 0.0032 [control vs. 3 mg/kg]). There was also more liver degeneration in the parenteral aluminum groups than the control group (1 [control], 2 [2 mg/kg], 2.5 [3 mg/kg], p = 0.0341 [control vs. 2 mg/kg] and 0.009 [control vs. 3 mg/kg]). However, there was no difference between 2 and 3 mg/kg AlCl3 for either variable. CONCLUSION: This study suggests that 4 weeks of parenteral aluminum can induce chronic inflammation and degeneration of the liver in rats. Therefore, we believe that daily injections of parenteral aluminum can produce a viable model of PNALD in rats. However, further studies are warranted, including measurement of serum aluminum levels in infants on PN.

Vacuum-assisted closure: a novel method of managing surgical necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) requiring surgical intervention is associated with mortality rates approaching 50%. We evaluated outcomes of patients that underwent surgical treatment for NEC with vacuum-assisted closure (VAC) of the abdomen as compared with traditional laparotomy, bowel resection, and ostomy creation. METHODS: A retrospective review identified 26 patients from 2007 to 2012 with NEC. Overall, 17 patients were treated with laparotomy, and 9 were treated with laparotomy and VAC (LapVac). Age, weight, preoperative and postoperative mean airway pressure, length of bowel resected, duration on total peripheral nutrition, time until initiation of feeds, and length of stay were assessed. A Student's t-test was used for statistical analysis. RESULTS: Nine LapVac patients underwent a total of 1.2 ± 1.3 VAC changes and had open abdomens for 13.1 ± 19.1 days. LapVac and traditional laparotomy patients had similar outcomes with respect to amount of bowel resected, time on a ventilator, time to initiation of feeds, and length of hospital stay. Two of nine patients (22%) in the LapVac group were placed in continuity without the need for an ostomy. We identified a subset of patients in the LapVac group that demonstrated signs of abdominal compartment syndrome (ACS), exhibiting mean airway pressures greater than 15 cm H2O preoperatively. Patients with ACS treated with VAC therapy had shorter time to initiation of feeds (p=0.047) and shorter lengths of stay (p=0.0395) as compared with traditional laparotomy. CONCLUSION: Our data demonstrate that use of the wound VAC is a safe approach in the management of premature infants with NEC requiring surgical intervention with outcomes comparable to standard surgical management. Use of the wound VAC may allow the establishment of bowel continuity and abdominal closure without the need for an ostomy. VAC therapy may also hasten the recovery of NEC patients with concomitant ACS by eliminating the compartment syndrome. Larger studies are required to confirm this theory.

Hepatocyte growth factor ameliorates inflammatory bowel disease in a rat model.

This study was designed to investigate the benefits of administration of hepatocyte growth factor in a rat model of inflammatory bowel disease. Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA-B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA-B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats received a 14-day infusion through an osmotic pump attached to a catheter positioned in either the jugular vein or the terminal ileum. Rats were evaluated for stool character, and gross and microscopic bowel inflammation. Statistics were analyzed using analysis of variance or the Kruskal-Wallis nonparametric test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats, intravenous administration of hepatocyte growth factor decreased diarrhea by 41% and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor exposure decreased total bowel lesions by 53% and microscopic inflammation by 40% compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on diarrhea. Administration of hepatocyte growth factor ameliorates many of the features of bowel disease in this rat model and theoretically could have therapeutic applications in the management of inflammatory bowel disease in humans.

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.

Maintaining a Sufficient and Quality Physician Workforce: The Role of For-profit Medical Schools.

Currently, in the United States there is a significant physician workforce shortage. This problem is likely to persist as there is no quick solution. The nature of this shortage is complex and involves factors such as an absolute physician shortage, as well as physician shortages in primary care and certain specialty care areas. In addition, there is a misdistribution of physicians to medically underserved areas and populations. The medical education system trains medical school graduates that eventually feed the physician workforce. However, several factors are in place which ultimately limits the effectiveness of this system in providing an appropriate workforce to meet the population demands. For-profit medical schools have been in existence in and around the continental US for many years and some authors have suggested that they may be a major contributor to the physician workforce shortage. There is currently one for-profit medical school in the US, however the majority exist in the Caribbean. The enrollment in and number of these schools have grown to partially meet the ever-growing demand for an increase in medical school graduates and they continue to provide a large number of graduates who return to the US for postgraduate medical training and, ultimately, increase the physician workforce. The question is whether this source will benefit the workforce quality and quantity needs of our growing and aging population.

Health care quality, access, cost, workforce, and surgical education: the ultimate perfect storm.

The discussions on health care reform over the past two years have focused on cost containment while trying to maintain quality of care. Focusing on just cost and quality unfortunately does not address other very important factors that impact on our health care delivery system. Availability of a well-trained workforce, maintaining the sophisticated medical/surgical education system, and ultimately access to quality care by the public are critical to maintaining and enhancing our health care delivery system. Unfortunately, all five of these components are under at risk. Thus, we have evolving the ultimate perfect storm affecting our health care delivery system. Although not ideal and given the uniqueness of our population and their expectations, our current delivery system is excellent compared to other countries. However, the cost of our current system is rising at an alarming rate. Currently, health care consumes 17% of our gross domestic product. If our system is not revised this will continue to rise and by 2025 it will consume 48%. The dilemma, given the current state of our overall economy and rising debt, is how to address this major problem. Unfortunately, the Affordable Care Act, which is now law, does not address most of the issues and the cost was initially grossly under estimated. Furthermore, the law does not address the issues of workforce, maintaining our medical education system or ultimately, access. A major revision of our system will be necessary to truly create a system that protects and enhances all five of the components of our health care delivery system. To effectively accomplish this will require addressing those issues that lead to wasteful spending and diversion of our health care dollars to profit instead of care. Improved and efficient delivery systems that reduce complications, reduction of duplication of tertiary and quaternary programs or services within the same markets (i.e. regionalization of care), health insurance reform, and tort reform collectively could save hundreds of billion dollars per year! These changes may not be easy to accomplish politically but will be essential to save what is likely the best health care system in the world.

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 Crohn's 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 Tukey's 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.

Vacuum-assisted closure in the treatment of extensive lymphangiomas in children.

BACKGROUND: The management of lymphangiomas in children is a complex problem with frequent recurrence and infection. Vacuum-assisted closure (VAC) devices have been shown to accelerate the healing of open wounds. We hypothesized that VAC therapy might decrease complications after resection of lymphangiomas. METHODS: A retrospective review was performed on 13 children (August 2005 to April 2010) who were patients undergoing lymphangioma resection with postoperative VAC therapy. Patient demographics, size and location of the lymphangioma, VAC duration and number of changes, hospital stay, complications, need for further surgery, and length of follow-up were recorded. RESULTS: Thirteen children (mean age, 8 years; mean weight, 34 kg) underwent 15 operations for lymphangiomas followed by postoperative VAC therapy. Locations included the head and neck, thorax and abdomen, and lower extremity. The mean VAC duration was 19 days, and they underwent a mean of 2.6 VAC changes. Six children had operative closure of the wound at a mean of 15 days postoperative. The remaining patients underwent closure by secondary intention. There were no recurrences. Complications included VAC device malfunctions requiring intervention and wound infections. Mean follow-up was 289 days. CONCLUSION: Postoperative VAC therapy for the treatment of lymphangiomas can be an effective adjunct to surgical treatment by decreasing risks of recurrence and infection.

Single-incision thoracoscopic surgery in children: equivalent results with fewer scars when compared with traditional multiple-incision thoracoscopy.

BACKGROUND: Single-incision pediatric endosurgery is gaining popularity, especially for abdominal operations. Several reports in the literature support the feasibility of the single-incision approach in pediatric laparoscopy. Here we compare our experience with single-incision thoracoscopic surgery (SITS) to traditional multiple-incision video-assisted thoracoscopic surgery (VATS) in children. METHODS: A chart review of all patients who underwent SITS at our institution was performed. The same number of demographically matched VATS case controls were selected from a pool of patients operated on during the same time period. Operative time, time until chest tube removal, length of stay, complications, and any need for further intervention were recorded. Statistical analysis was done by Student's t-test using Instat 3. RESULTS: Fourteen SITS procedures were performed during the study period. These patients were compared with 14 VATS case controls. Both groups were similar with regard to age, weight, sex, and procedures performed. The mean operative time in the SITS group was 84 ± 43 minutes versus 64 ± 30 in the VATS group (P=.18). Days until chest tube removal was 4 ± 2.2 in the SITS group and 2.8 ± 1.4 in the VATS group (P=.09). Length of hospital stay was 5.5 ± 4.4 days in the SITS group versus 7.2 ± 8.6 in the VATS group (P=.51). There were no intraoperative complications and no procedure conversions in either group. One SITS patient who underwent a wedge resection and mechanical pleurodesis for a spontaneous pneumothorax was readmitted for a recurrent pneumothorax and required a reoperation. CONCLUSIONS: Our experience demonstrates that there are no statistically significant differences in operative time, time until chest tube removal, and length of hospital stay when comparing SITS to VATS in children. We believe that SITS is an equivalent procedure that allows for fewer scars when compared with traditional multiple-incision VATS in children.