Eric M. Webber

Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration.

During liver regeneration quiescent hepatocytes undergo one or two rounds of replication and then return to a nonproliferative state. Growth factors regulate this process by providing both stimulatory and inhibitory signals for cell proliferation. EGF, TGFα, and HGF stimidate DNA synthesis in hepatocytes in vivo and in culture but the sensitivity of cidtured hepatocytes to the mitogenic effects of these factors is much higher than that of quiescent hepatocytes in intact livers. We have proposed that after partial hepatectomy, hepatocytes enter a state of replicative competence (“priming”) before they can fully respond to growth factors. The priming step is an initiating event in liver regeneration that involves the activation and DNA binding of NF‐κB and other transcription factors, which could be induced by TNF or other cytokines. EGF, TGFα, and HGF have major effects on liver growth. TGFα expression correlates with hepatocyte DNA synthesis during liver development and growth and the constitutive expression of the factor confers proliferative activity to adult hepatocytes in vivo and in culture. The data indicate that the activity of stimulatory and inhibitory growth factors such as TGFβl and activin is low in normal livers but that the expression of both types of factors increase during liver regeneration.—Fausto, N., Laird, A. D., Webber, E. M. Role of growth factors and cytokines in hepatic regeneration. FASEB J. 9, 1527‐1536 (1995)

Long-term bowel function and quality of life in children with Hirschsprung's disease.

BACKGROUND/PURPOSE Little is known about the quality of life (QOL) of children with Hirschsprungs disease (HD) as they grow older. The purpose of this study was to measure the QOL and bowel function of these children as they mature. METHODS All children who were surgically treated for HD at British Columbia Childrens Hospital, Vancouver, British Columbia, Canada between 1986 and 2003 were invited to participate. Each family was sent 3 previously validated questionnaires exploring current QOL and bowel function. RESULTS Fifty-one families participated (49%), with children between the ages of 3 and 21 years. Fecal continence improved significantly with age (P = .04) and was the strongest predictor of QOL scores of all variables in our study. There was no statistically significant difference in QOL scores between children with HD and healthy children, although a clinically relevant impairment in QOL may be present, especially in psychosocial scores. CONCLUSIONS Fecal continence is an important predictor of overall QOL in children surgically treated for HD. Although continence tends to improve with age, a number of older children still have ongoing continence problems, and they seem to be a group at risk for impaired QOL. Our study indicates that interventions for children with incontinence may offer gains in QOL as well as bowel function.

Comparative genomic hybridization detects multiple chromosomal amplifications and deletions in undifferentiated embryonal sarcoma of the liver

Undifferentiated embryonal sarcoma (UES) is the third most common hepatic malignancy in children. Previous reports have described a broad range of complex cytogenetic abnormalities in individual cases of hepatic UES. Herein we report the cytogenetic findings of six cases of hepatic UES at our institution analyzed by conventional cytogenetic methods and comparative genomic hybridization (CGH). The CGH demonstrated several chromosomal gains and deletions in each case, but there was no specific abnormality seen in every case. Patterns of chromosomal changes included gains of chromosome 1q (four cases), 5p (four cases), 6q (four cases), 8p (three cases), and 12q (three cases), and losses of chromosome 9p (two cases), 11p (two cases), and chromosome 14 (three cases). The three cases in which CGH showed gains in the 12q region were studied specifically for amplifications of MDM2 and CDK4, two genes that have been shown to be amplified in other soft tissue sarcomas. However, Southern analysis showed no amplification of MDM2 or CDK4 in these three cases. Further analysis will be needed to determine the critical events in the pathogenesis of these malignant pediatric liver tumors.

Tetralogy of Fallot With Total Anomalous Pulmonary Venous Drainage and Esophageal Atresia: Complete Correction in Infancy

We report an infant with tetralogy of Fallot, total anomalous pulmonary venous drainage, and esophageal atresia with tracheoesophageal fistula who underwent successful complete repair of all lesions in the newborn period.

Laparoscopy as a Cause of a False-Positive Meckel's Scan

A new cause of a false-positive result of a Meckels scan is reported. An 11-year-old girl had a 3-week history of constant right lower quadrant pain that was initially managed by laparoscopic appendectomy. A repeated laparoscopy for persistent pain was nondiagnostic. A missed Meckels diverticulum was considered as the cause of this pain, which prompted a Meckel scan. This scan revealed a periumbilical focus of activity that was interpreted as a Meckels diverticulum attached to the anterior abdominal wall by a band. The laparotomy showed no Meckels diverticulum. The false-positive result of the Meckel scan may be the result of inflammation from the periumbilical laparoscopic port site.

Dumbbell metastatic cystosarcoma phyllodes of the heart and lung

Cystosarcoma phyllodes is an uncommon breast tumor that rarely metastasizes. A case of dumbbell cystosarcoma phyllodes metastatic to the heart and lung diagnosed antemortem is described. The roles of diagnostic echocardiography and surgical excision are discussed. Atrial extension of a lung malignancy through a pulmonary vein is not an absolute contraindication to operation, but careful patient selection and operative planning are required.

Helicobacter pylori is not associated with nonspecific abdominal pain in children

Nonspecific abdominal pain is a significant problem in the pediatric population, and there has been much recent interest in the role that Helicobacter pylori (HP) might play in this disorder. A retrospective review was conducted at our center to determine its prevalence among children with otherwise undiagnosed abdominal pain. The study was conducted over a 45-month period during which 47 patients underwent gastroscopy and antral biopsies in the workup of this problem. Of the 37 patients who did not have a history of acid-pepsin disease (APD), only one (2.7%) tested positive for HP. In contrast, of the 10 who had a history of APD, three (30%) tested positive (P < .03). There were no distinguishing features among the HP-positive patients except for the presence of associated antral gastritis. Based on the current endoscopic results, of the nine patients with current evidence of APD, four (44%) were positive for HP; of the other 38 patients, none was positive for HP. Therefore, HP appears to be associated with antral gastritis, and HP does not play a role in nonspecific abdominal pain in this population.

The surgical personality: comparisons between urologists, non-urologists and non-surgeons

BACKGROUND : Our objective was to compare personality traits between urologists and other surgeons, as well as between surgeons and non-surgeons. METHODS : Eighty-six surgeons (57 faculty, 29 residents) completed the Revised NEO Personality Inventory (NEO PI-R), a validated measure of normal personality traits. Subjects agree or disagree with 240 statements to generate a score in each of the 5 major character traits: extraversion (E), openness (O), conscientiousness (C), agreeableness (A) and neuroticism (N). Each factor is subdivided into 6 component facets. Scores for urology faculty and residents were compared to the other surgical groups and 21 pediatricians. RESULTS : The 3 groups differed significantly on extraversion (p < 0.001). Post-hoc analyses indicated that urologists obtained significantly higher extraversion scores than other surgeons (p < 0.05) and non-surgeons (p < 0.001) Other surgeons also scored significantly higher than non-surgeons on the extraversion factor (p < 0.05). No significant differences emerged on openness, conscientiousness, agreeableness or neuroticism. Of the 6 extraversion facets, urologists obtained significantly higher scores on gregariousness and excitement-seeking (p < 0.05) than non-urologist surgeons, and significantly higher scores on gregariousness (p < 0.05), activity (p < 0.01), excitement seeking (p < 0.001), and positive emotions (p < 0.05) than non-surgeons. Non-urologist surgeons obtained significantly higher scores than non-surgeons on Activity and Excitement-seeking (p < 0.01).There were no significant differences in the facets of warmth or assertiveness. INTERPRETATION : Urologists appear to be more extraverted compared to other surgeons. Both groups of surgeons were more extraverted than non-surgeons. If these findings can be confirmed on a wider basis, the data may be helpful in resident selection, mentoring, evaluation and career counselling.

Perianal Ependymoma Presenting in the Neonatal Period

Extraspinal ependymomas are a rare type of glioma that may arise in the sacrococcygeal region, presenting as a pelvic mass in an infant or child. Ependymoma presenting in the newborn period has not been described previously. Herein we describe a case of a newborn boy who presented with a perianal ependymoma, which was subsequently found to have presacral extension. The major diagnostic challenge this case presented was to rule out the alternative diagnosis of sacrococcygeal teratoma or a developmental malformation/heterotopia.

Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor

We used KO mice lacking either TNF receptor 1 (TNFR-1) or receptor 2 (TNFR-2) to determine whether signaling at the start of liver regeneration after partial hepatectomy (PH) involves only one or both TNF receptors and to analyze in more detail the abnormalities caused by lack of TNFR-1 receptor, which is required for the initiation of liver regeneration. Lack of TNFR-2 had little effect on NF-kappaB and STAT3 binding, and no effect in interleukin-6 production after PH, but caused a delay in AP-1 and C/EBP binding and in the expression of c-jun and c-myc messenger RNA (mRNA). In contrast to mice lacking TNFR-1, which had deficient hepatocyte DNA synthesis and massive lipid accumulation in hepatocytes, TNFR-2 KO mice had normal liver structure and similar levels of hepatocyte DNA replication as those of wild type mice. We conclude that TNFR-1, but not TNFR-2, is necessary for liver regeneration, and that NF-kappaB and STAT3 binding are activated by signals transduced by TNFR-1. Inhibition of AP-1 and C/EBP binding and in the expression of c-jun and c-myc mRNA in the first 4 hours after PH, as well as the apparent lack of Fos in AP-1 complexes, had no effect on the timing or extent of DNA replication.