Ileocecal Burkitt's lymphoma presenting as ileocolic intussusception with appendiceal invagination and acute appendicitis.

Intussusception is a common cause of abdominal pain in children. Although most cases are idiopathic, about 10% of cases have a pathologic lead point. Burkitt's lymphoma is not a common etiology. Burkitt's lymphoma might present primarily as intussusception in children but has rarely been associated with appendicitis. We report a case in which a 10-year-old obese boy who initially presented with acute appendicitis due to ileocolic intussusception with appendiceal invagination. He underwent one-trocar laparoscopy and antibiotic treatment. The symptoms recurred 10 days after discharge. Colonoscopy disclosed ileocecal Burkitt's lymphoma as the pathological lead point. This case emphasizes the importance of the age of the patient and the anatomic location of the intussusception related to possible etiology, and hence the most appropriate surgical procedure.

Characterization of plasma proteome in biliary atresia.

BACKGROUND: Biliary atresia (BA) is a disorder during infancy with unknown etiology in which progression frequently leads to liver cirrhosis. Plasma proteome is characterized in this study. METHODS: Twelve paired plasma samples from 6 children with BA who received surgical correction at early stage and then liver transplantation at late stage of liver cirrhosis were studied. Plasma samples from 2 subjects without liver disorder were used as normal reference for 2-dimensional gel electrophoresis and for identification of protein spots by mass spectrometric analysis. Plasma samples from another 3 normal subjects (with a total of 5) were used for nephelometric quantification of immunoglobulin kappa light chain in comparison with patients' samples. RESULTS: Among the protein spots detected, ranging from 6 to 200 kDa mass with pIs of 3-10, significant up-regulation of immunoglobulin kappa light chain was found at the late stage of BA, which was subsequently confirmed by nephelometric analysis. Conversely, significant decrease of apolipoprotein (Apo) A-I and C-II, haptoglobin alpha2 and beta chain, and transthyretin were detected during the progression of BA. CONCLUSIONS: Increased immunoglobulin kappa light chain detected in late-stage BA characterizes adverse immune modulation in this disorder. Decreased apolipoproteins, haptoglobin and transthyretin levels might be potential markers of progressive liver injury, fibrosis and defective lipid metabolism in BA.

Upstream stimulatory factor 2 is implicated in the progression of biliary atresia by regulation of hepcidin expression.

BACKGROUND: Hepcidin is downregulated during the progression of biliary atresia (BA), but the mechanism is still unknown. METHODS: We analyzed single nucleotide polymorphism of rs7251432 and 916145 within hepcidin and its upstream, USF2 gene, respectively, in 52 patients of BA and 96 healthy controls. Liver tissues were obtained from 10 patients with early and late stage of BA, 10 patients with choledochal cyst, and 4 normal controls to study upstream stimulatory factor 2 (USF2) messenger RNA (mRNA) and protein expressions. Chromatin immunoprecipitation assay and USF2-specific short interference RNA (siRNA) were used in human HepG2 cells to show that USF2 can regulate hepcidin expression. RESULTS: C and CC allele frequencies of rs916145 of USF2 were significantly higher in patients with BA than in healthy controls. There was also significantly higher USF2 protein nuclear translocation in the early stage of BA than in the late stage, which was compatible with higher hepcidin mRNA expression in the early stage of BA. Chromatin immunoprecipitation assay demonstrated physiologic bindings of USF2 to the hepcidin promoter in HepG2 cells. USF2 siRNA also significantly knocked down hepcidin mRNA expression. CONCLUSION: The study demonstrates that C allele of rs916145 in USF2 gene has more frequency for developing BA, and decreased USF2 protein nuclear translocation might partly play a role in the decreased hepcidin expression in the cholestatic liver injury of the late stage of BA.

Evaluation of hepatocyte growth factor in patients with biliary atresia.

BACKGROUND: Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes in primary culture and seems to be a trigger factor for liver regeneration and proliferation after liver injury. The aim of this study was to evaluate the expression of HGF in patients with biliary atresia (BA). METHODS: Plasma levels of HGF were determined using an enzyme-linked immunosorbent assay from 19 patients with BA, 10 at the time of Kasai procedure (KP) and 9 at liver transplantation (LT), and 10 patients with nonicteric choledochal cyst served as control. Hepatic HGF level was quantitatively estimated using enzyme-linked immunosorbent assay and Western blotting. Hepatocyte growth factor messenger RNA (mRNA) expression of liver was measured with quantitative reverse transcriptase polymerase chain reaction. Immunohistochemical study of liver sections was evaluated by HGF staining. RESULTS: Plasma HGF levels in LT patients were significantly higher than in KP patients (2977.30 +/- 1251.42 vs 960.17 +/- 559.82 pg/mL, P < .01). Western blots showed increased hepatic HGF levels in LT group than in KP group (2.02 +/- 0.86 vs 1.44 +/- 0.72 pg/mug total protein, P < .05). However, there were no differences in HGF mRNA expression. Immunohistochemical study showed significantly increased HGF staining in hepatocytes of LT livers than of KP livers. CONCLUSIONS: Elevation of plasma and liver HGF levels could be related to the progression of liver cirrhosis in patients with BA. Hepatocyte growth factor might have a protective role, probably through the induction of hepatocyte proliferation, during the development of BA-associated liver cirrhosis.

Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration in cholestatic rats receiving biliary intervention.

AIM: Biliary intervention may augment chemokine expression and inflammatory cell infiltration and aggravates liver injury in cholestatic rats. We tested the efficacy of glucocorticoid pretreatment to prevent the complications. METHODS: A model of biliary intervention was established in rats without (sham) or with bile duct ligation (BDL). Before biliary intervention, rats were randomly assigned to receiving intravenous injection of dexamethasone (DX group) or normal saline (NS group). Plasma levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were measured with enzyme-linked immunosorbent assay, and liver messenger RNA of these chemokines was quantified with real-time quantitative reverse transcriptase-polymerase chain reaction. Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase, respectively. RESULTS: By 3 hours after biliary intervention, plasma MCP-1 and MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3 hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes returned to baseline levels by 24 hours. CONCLUSION: Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration, which may consequently alleviate liver injury in cholestatic rats receiving biliary intervention.

Developmental anomalies and disabilities associated with hypospadias.

PURPOSE: The incidence of developmental anomalies and disabilities associated with hypospadias is still a matter of controversy and data on this issue are sparse. We describe our experience with and evaluation of developmental anomalies and disabilities in a population in which posterior hypospadias was the most common anomaly. MATERIALS AND METHODS: We reviewed the records of 356 patients who underwent hypospadias repair from January 1986 through April 2000. Collected data included the Barcat classification of the hypospadias anomaly, anatomical penile variants, associated urogenital and extra-urogenital anomalies, and associated disabilities of physical and mental development. RESULTS: Of the 356 patients 234 (65.7%) had posterior, 88 (24.7%) anterior and 34 (9.6%) mid hypospadias. Anatomical variants, including penoscrotal transposition, bifid scrotum and micropenis, occurred predominantly in patients with posterior hypospadias, while penile torsion was present exclusively in the other 2 groups. Inguinal hernia, which was the most common urogenital anomaly, was distributed evenly among the 3 groups with a prevalence rate of 12.4%. Undescended testis in 26 cases (7.3%) was most often associated with posterior hypospadias. In order of frequency associated extra-urogenital anomalies included congenital heart disease in 19 cases (5.3%), musculoskeletal anomalies in 11 (3.1%), anorectal malformation in 6 (1.7%), cleft palate in 3 and other in 7. In 21 patients (5.9%) associated disorders were related to physical and mental development, including growth retardation in 6, cerebral palsy in 2 and psychological disorders that significantly impaired patient bodily function, behavior and performance in 11. Most extra-urogenital anomalies or disorders were associated with posterior hypospadias. CONCLUSIONS: Posterior hypospadias was the most common anomaly in this study. It was associated with a high rate of extra urogenital anomalies, and physical and psychosocial disabilities. The significance of the latter findings with respect to the development of affected patients needs further clarification.

Identification of transforming growth factors actively transcribed during the progress of liver fibrosis in biliary atresia.

BACKGROUND/PURPOSE: Transforming growth factor-beta (TGF-beta) 1 and 2 and their receptors TbetaR-I, TbetaR-II, and TbetaR-III are powerful profibrogenic mediators in the body. Their expression has not been completely elucidated in the progress of liver fibrosis associated with biliary atresia (BA). METHODS: The authors compared the cytokine expression in the liver of 3 patients with BA at Kasai's procedure (KP) and in 3 patients at liver transplantation (LT). Two liver samples from children with no liver disorders served as normal controls (CO). Real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) was used to confirm the findings of relative mRNA expression of TGF-beta1 and 2 and their receptors. An immunohistochemistry and an enzyme-linked immunoassay (ELISA) were used to localize the liver cells that express TGF-beta2 and to quantitate the protein expression among groups. RESULTS: Compared with controls, both TGF-beta1 and TGF-beta2 mRNA expression increased in the liver during the progress of liver fibrosis in patients with KP and LT on the array. Only TGF-beta2 showed a significant increase in expression in LT compared with KP and CO (P =.001 for TGF-beta2 and P = 0.054 for TGF-beta1). Both TbetaR-I and TbetaR-II showed no significant change among groups; TbetaR-III decreased significantly in LT compared with CO (P =.011). TGF-beta2 immunostaining was mainly localized in the bile duct epithelium and was remarkably higher in LT in which the proliferating bile ductules and the hepatocytes contributed to the increase in immunostaining and possibly to significantly higher plasma TGF-beta2 protein levels in LT than in KP. CONCLUSIONS: This study identified TGF-beta2 as the most actively transcribed TGF-beta gene during the progress of liver fibrosis in BA and found a reciprocal relationship of upregulation of TGF-beta2 with downregulation of TbetaR-III in LT.

The human Delta-like 1 homologue is implicated in the progression of liver fibrosis in biliary atresia.

Advanced liver cirrhosis frequently occurs in infants with biliary atresia despite early surgical correction. The aetiology is unknown, but may involve many cytokines and liver cells including hepatic stellate cells (HSCs). A cytokine expression array and real-time quantitative reverse transcription-polymerase chain reaction (QRT-PCR) were used to study cytokine expression during the progression of liver fibrosis in biliary atresia. A Delta-like 1 homologue (DLK1) gene was identified and this gene was up-regulated during the early stage, and down-regulated during the late stage, of biliary atresia, similar to the expression pattern of the procollagen alpha1(I) gene. Further characterization with immunohistochemistry, confocal microscopy, and in situ hybridization revealed that the DLK1 protein was mainly present in the cytoplasm of smooth muscle actin-positive mesenchymal cells that were morphologically and immunohistochemically identical to activated HSCs/myofibroblasts, whereas DLK1 mRNA was present only in hepatocytes. As DLK1 is a negative regulator of adipocyte differentiation and may control cell fate during differentiation, overexpression of DLK1 protein in HSCs in the early stage of biliary atresia suggests that DLK1 may be implicated in the transformation of HSCs from fat-storing cells to myofibroblasts and in fibrogenesis associated with biliary atresia.