Thirty-day outcomes for children and adolescents undergoing laparoscopic sleeve gastrectomy at a free-standing children's hospital.

The obesity epidemic continues to affect millions of children and adolescents. Non-surgical options do not result in significant or sustained weight loss; thus bariatric surgery has become increasingly utilized. Limited data exist regarding safety for paediatric bariatric surgery, especially outside of National Institutes of Health (NIH)-funded centres. We hypothesized that the perioperative outcomes of paediatric patients undergoing laparoscopic sleeve gastrectomy (LSG) at our free-standing children's hospital would provide adequate safety profiles. We retrospectively reviewed demographics, comorbidities and 30-d outcomes for all patients who underwent LSG from 2010 to 2015 at a free-standing children's hospital. A total of 105 patients underwent 107 LSG procedures (two revisions). Mean age was 17.2 ± 2.4 years. Male to female ratio was 1:4. The majority were Black (57.1%), followed by White (21.0%) and Hispanic (18.1%). The mean body mass index was 51.0 ± 9.8 kg/m2 . Comorbidities included obstructive sleep apnea (59.0%), hypertension (15.2%), polycystic ovarian disease (16.7% of females only), depression (12.4%) and diabetes (11.4%). Median length of stay was 2.0 d (1-7 d). There were no deaths. Major complications occurred in four patients (3.8%); three required reoperation. Four patients (3.8%) experienced minor complications. Laparoscopic sleeve gastrectomy can be safely performed for children and adolescents at a free-standing children's hospital without NIH-support.

Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity.

BACKGROUND: The surgical treatment of obesity in the high-risk, high-body-mass-index (BMI) (>60) patient remains a challenge. Major morbidity and mortality in these patients can approach 38% and 6%, respectively. In an effort to achieve more favorable outcomes, we have employed a two-stage approach to such high-risk patients. This study evaluates our initial outcomes with this technique. METHODS: In this study, patients underwent laparoscopic sleeve gastrectomy (LSG) as a first stage during the period January 2002-February 2004. After achieving significant weight loss and reduction in co-morbidities, these patients then proceeded with the second stage, laparoscopic Roux-en-Y gastric bypass (LRYGBP). RESULTS: During this time, 126 patients underwent LSG (53% female). The mean age was 49.5 +/- 0.9 years, and the mean BMI was 65.3 +/- 0.8 (range 45-91). Operative risk assessment determined that 42% were American Society of Anesthesiologists physical status score (ASA) III and 52% were ASA IV. The mean number of co-morbid conditions per patient was 9.3 +/- 0.3 with a median of 10 (range 3-17). There was one distant mortality and the incidence of major complications was 13%. Mean excess weight after LSG at 1 year was 46%. Thirty-six patients with a mean BMI of 49.1 +/- 1.3 (excess weight loss, EWL, 38%) had the second-stage LRYGBP. The mean number of co-morbidities in this group was 6.4 +/- 0.1 (reduced from 9). The ASA class of the majority of patients had been downstaged at the time of LRYGB. The mean time interval between the first and second stages was 12.6 +/- 0.8 months. The mean and median hospital stays were 3 +/- 1.7 and 2.5 (range 2-7) days, respectively. There were no deaths, and the incidence of major complications was 8%. CONCLUSION: The staging concept of LSG followed by LRYGBP is a safe and effective surgical approach for high-risk patients seeking bariatric surgery.

Characterization of an aFGF gene expression vector with therapeutic potential.

BACKGROUND: Topical application of growth factors to wounds has proven to be suboptimal in achieving epithelial growth and accelerating healing. We propose transfection of fibroblasts with a gene for acidic fibroblast growth factor (aFGF) which will allow continuous, local delivery of the growth factor to wounds, ulcerative lesions, or healing tissues. METHODS: We utilized a pMEXneo vector containing the human aFGF gene with a secretory signal sequence from the hst/KS3 gene to obtain continuous secretion of therapeutic doses of aFGF. NIH 3T3 fibroblasts were transfected using a liposomal transfection reagent and grown in selective media. RESULTS: Dot blot hybridization with labeled complementary DNA probes revealed the presence of plasmid DNA in transfected but not wild type fibroblasts. Intracellular concentrations of aFGF remained low in transfected cells; however, the media contained high levels (32 +/- 7 nM) of aFGF as measured by ELISA. Concentrations of aFGF capable of stimulating cell proliferation were maintained for several weeks. CONCLUSIONS: The aFGF cDNA was transcribed and translated into a functional polypeptide that is secreted from NIH 3T3 cells at physiologically significant concentrations. Stable transfection with a eukaryotic vector which induces secretion of aFGF at levels promoting cell growth holds promise for clinical application in wounds or healing tissue. Transfection could be achieved by topical or endoscopic injection of this type of vector.

Role of insulin-like growth factor-I in esophageal mucosal healing processes.

The current study examines the stimulation of healing processes and signal transduction that is mediated by insulin-like growth factor-I (IGF-I) in an ex vivo esophageal explant model when using tyrphostin inhibition of receptor tyrosine kinase. The explant model provides a 3-dimensional cellular environment of multiple interacting cells isolated from the neural and vascular supply. Tyrphostins previously characterized for their interactions with epithelial growth factor (EGF) receptor-associated protein tyrosine kinases were tested for their potential effects on IGF-I growth-promoting activity. Explants of rabbit esophagus were incubated in media with or without IGF-I. Tyrphostins 1, 23, 25, 46, 47, 51, and 63 were added. We assessed DNA synthesis by tritiated thymidine incorporation. Outgrowth from the edge of the primary mucosa of the explant was evaluated on histologic sections, and cell proliferation was confirmed with immunohistology. IGF-I increased the incorporation of tritiated thymidine by 50% to 100%. Tyrphostins 23 and 47 eliminated IGF-I-induced proliferation in a dose-dependent manner. Tyrphostins 25, 46, and 51--along with negative controls tyrphostin 1 and tyrphostin 63--were ineffective, inasmuch as IGF-I-stimulated growth remained unchanged in their presence. Proliferative activity demonstrated by PCNA staining was confined to new mucosa. Two of 5 tyrphostins originally developed as EGF receptor protein tyrosine kinase inhibitors were effective in inhibiting the actions of exogenous IGF-I. We conclude that IGF-I stimulation may play an important role in repair processes in the esophagus and that this stimulation can be inhibited by using specific tyrphostins.

EGF and IGF-I synergistically stimulate proliferation of human esophageal epithelial cells.

Proliferation of esophageal mucosal cells is important in repair of reflux-induced injury. We studied the effects of EGF, IGF-I, and IGF-I/binding protein-3 (BP-3) complex on immortalized esophageal epithelial (HET-1A) cells and searched for synergy between the growth factors. HET-1A cells were plated at 5 x 10(4) in 12 well plates. After 2 days in optimal media, they were maintained in basal media with or without the test peptides: EGF at 0.05-5 nM, IGF-I at 0.1-10 nM, IGF-I/BP-3 at 0.1-10 nM, and a combination of EGF at 5 nM and IGF-I or IGF-I/BP-3 at 1 and 10 nM. In comparison to basal media EGF and IGF-I stimulated cell proliferation over baseline at 5 and 10 nM, respectively. The combination of EGF at 5 nM and IGF-I at 1 and 10 nM worked synergistically, increasing cell counts over baseline to 10.3 +/- 0.2 and 14.6 +/- 0.8 x 10(5), respectively. The calculated additive effect of EGF and IGF-I at 1 and 10 nM individually increased cell counts to 8.2 +/- 0.2 and 10.4 +/- 0.6 x 10(5), respectively. The difference between the observed and the calculated values was significant at P < 0.05, ANOVA, Turkey test. IGF-I/BP-3 complex enhanced this synergy at low levels of IGF-I but not at 10 nM IGF-I. EGF, IGF, and IGF-I/BP-3 independently promote HET-1A proliferation. IGF and EGF in combination demonstrate synergism with potentiated interaction presumably because of their different roles in the cell cycle, EGF being a competence factor and IGF being a progression factor. This combination may have potential as a treatment for esophageal mucosal injury, and IGF-I/BP-3 may further enhance their benefit.