Model to estimate abdominal wall thickness in children undergoing placement or replacement of gastrostomy devices.

OBJECTIVES: Abdominal wall thickness (AWT) is a key measurement when placing or replacing low profile gastrostomy devices. This measurement varies, depending on nutritional status and body habitus. We developed a mathematical model to estimate AWT using a compendium of body measurements. METHODS: Ultrasonography was used to measure AWT at the initial gastrostomy site in subjects aged 22 days to 24 years old. Other body measurements (height, weight, waist circumference and distance from xiphisternum to pubis) were also obtained. Multiple linear regression was used to develop two separate models using age of 2 years to separate the groups. For analysis, AWT is log transformed. RESULTS: Data from 97 subjects were used for analysis. The final model for those ≤24 months old is the following: ln(Estimated AWT) = -1.255 + 0.082*(1 if age 3-24 months, 0 if <3 months) + 0.022*(waist circumference in cm). The final model for those >24 months old is the following: ln(Estimated AWT) = -1.335 + 0.271*(1 if age >84 months, 0 if 24-84 months) + 0.082*(BMI) CONCLUSION: This model to estimate AWT is useful for determining the length of a gastrostomy device at initial placement and with subsequent changes. More data are needed to refine and further validate the model. LEVEL OF EVIDENCE: Level IV, study of prognostic test.

Laparoscopic-Assisted Endoscopic Resection of a Gastric Leiomyoma.

Leiomyomas are infrequent benign intestinal tumors that can arise at any age and location within the gastrointestinal (GI) tract. These tumors can cause symptoms including abdominal pain, obstruction, intussusception, volvulus, GI bleeding, or amass and should be resected if symptomatic. Open surgical resection is considered the standard for removing these tumors. However, recent improvements in endoscopic and laparoscopic equipment have made it possible to utilize minimally invasive techniques of tumor removal including complete endoscopic resection or endoscopic-assisted laparoscopic resection. We present the case of an adolescent female with a large mass located at the gastroesophageal junction (GEJ) causing GI bleeding. Given the location of the mass near the GEJ and the morbidity associated with surgical resection, we performed laparoscopic-assisted complete endoscopic resection of tumor. In addition, this tumor had an unusual immunohistochemical-staining pattern, with focal expression of markers more often seen in GI stromal tumors, elucidating a gray area between these two tumor classes with potential implications for patient follow-up. Laparoscopic-assisted endoscopic resection of benign tumors is a useful technique that can be employed to facilitate resection of mucosal and subserosal masses near the GEJ with minimal morbidity.

Human hepatic mitochondria generate reactive oxygen species and undergo the permeability transition in response to hydrophobic bile acids.

OBJECTIVES: Hydrophobic bile acids accumulate in the liver during cholestasis and are believed to cause hepatocellular necrosis and apoptosis in part through induction of the mitochondrial permeability transition (MPT) and the mitochondrial generation of oxidative stress. The purpose of this study was to determine if human hepatic mitochondria respond to bile acids in this manner. METHODS: The MPT was measured spectrophotometrically and morphologically in normal human liver mitochondria exposed to glycochenodeoxycholic acid (GCDC) with and without cyclosporin A, an inhibitor of the MPT, antioxidants, and tauroursodeoxycholic acid (TUDC). Hydroperoxide generation was measured by dichlorofluorescein fluorescence. Cytochrome c and apoptosis-inducing factor were assessed by immunoblotting. RESULTS: GCDC induced the MPT in a dose-dependent manner, which was inhibited by cyclosporin A, alpha-tocopherol, beta-carotene, idebenone, and TUDC. GCDC stimulated reactive oxygen species generation and release of cytochrome c and apoptosis-inducing factor, which were significantly inhibited by the antioxidants, cyclosporin A, and TUDC. CONCLUSIONS: Mitochondrial pathways of cell death are stimulated in human hepatic mitochondria exposed to GCDC consistent with the role of mitochondrial dysfunction in the pathogenesis of cholestatic liver injury. These results parallel those reported in rodents, supporting the extrapolation of mechanistic studies of bile acid toxicity from rodent to humans.

Increased susceptibility of fat-laden Zucker-rat hepatocytes to bile acid-induced oncotic necrosis: an in vitro model of steatocholestasis.

UNLABELLED: Metabolic liver disorders cause chronic liver disease and liver failure in childhood. Many of these disorders share the histologic features of steatosis and cholestasis, or steatocholestasis. In this study we sought to (1) develop an in vitro model of steatocholestasis, (2) determine the mechanisms of cell death in this model, and (3) determine the role of mitochondrial disturbances in this model. METHODS: Hepatocytes were isolated from 8-week-old obese (fa/fa) and lean Zucker rats. Cell suspensions were treated with glycochenodeoxycholic acid (GCDC), after which reactive oxygen species (ROS) generation, oncotic necrosis, apoptosis, and ATP content were assessed. Isolated liver mitochondria were exposed to GCDC and analyzed for ROS generation, mitochondrial membrane-permeability transition (MPT), and cytochrome c release. Oncotic necrosis was significantly increased and apoptosis reduced in fa/fa hepatocytes exposed to GCDC compared with that in lean hepatocytes. Necrosis occurred by way of an ROS- and MPT-dependent pathway. Basal and dynamic ATP content did not differ between fa/fa and lean hepatocytes. GCDC stimulated ROS generation, MPT, and cytochrome c release to a similar extent in purified mitochondria from both fa/fa and lean rats. These findings suggest that fat-laden hepatocytes favor a necrotic rather than an apoptotic cell death when exposed to low concentrations of bile acids. The protective effects of antioxidants and MPT blockers suggest novel therapeutic strategies for the treatment of steatocholestatic metabolic liver diseases.

Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger.

OBJECTIVE: To test the hypothesis that there is an improved response to interferon in children with chronic hepatitis B (HBV) who are < or =5 years of age. STUDY DESIGN: Retrospective chart review of 22 consecutive children with chronic HBV (ages 17 months to 17 years; median, 83.9 months; 14 male, 8 female) treated with interferon-alpha2b. RESULTS: Ten patients (48%) responded to treatment [HBeAg (-), Anti-HBe (+), HBV DNA (-), HBsAg (+) and normal alanine aminotransferase/aspartate aminotransferase (ALT/AST) at 6 months after treatment], and 5 seroconverted HBsAg [above plus HBsAg negative and anti-HBs (+)]. Seven of 9 patients (78%) < or =5 years of age responded (5 cleared HBsAg). Three of 13 patients (23%) >5 years of age responded. Patient age at treatment was significantly lower in responders (63 +/- 70 months) versus nonresponders (104 +/- 55 months, P =.005). AST, ALT, and HBV DNA at the start of treatment were not different between responders and nonresponders or between patients < or =5 and >5 years old. CONCLUSIONS: Interferon treatment may be more effective in younger children with chronic hepatitis B.