Pancreatic ascites and Pleural Effusion in Children: Clinical Profile,Management and Outcomes

BackgroundPancreatic ascites (PA) and pleural effusion (PPE) are rarely encountered in children. They develop due to disruption of the pancreatic duct (PD) or leakage from an associated pancreatic fluid collection (PFC). The literature on childhood PA/PPE and its management is scarce.MethodsA retrospective review of children with PA/PPE diagnosed and managed at our center over the last 4 years was performed. The clinical, biochemical, radiological and management profiles were analyzed. Conservative management included nil per oral, octreotide and drainage using either percutaneous catheter or repeated paracentesis. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) and transpapillary stenting.ResultsOf the 214 children with pancreatitis, 15 (7%) had PA/PPE. Median age was 9 years with a third under 2 years. Median ascitic fluid amylase was 8840 U/L and all had elevated protein (>2.5 g/dl) and low serum ascites-albumin gradient ascites (<1.1). While PA/PPE was the first manifestation of underlying chronic pancreatitis (CP) in 10 children (67%), trauma was seen in 4 (26%) and hypertriglyceridemia in 1 (7%). On imaging, PD disruption could be identified in 10 (67%) children. ERCP and stenting was done in 10 children. Conservative management alone (n = 4) and endotherapy (n = 10) was successful in 93% with only one requiring surgery. The younger children (n = 4), were managed conservatively and only 1 of them required surgery. Resolution of PA/PPE was achieved in all with no recurrences.ConclusionsConservative management and ERCP plus transpapillary stenting results in resolution of majority of pediatric PA/PPE. Children presenting with PA/PPE needs to be evaluated for CP.     

Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)--mediated cytotoxicity by selective up-regulation of TRAIL-R1

Cytotoxic activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand), used alone or in different combinations with either a low (1.5 Gy) or a high (15 Gy) single dose of ionizing radiation (IR), was investigated on erythroleukemic cells (K562, HEL, Friend, primary leukemic erythroblasts) and on primary CD34(+)-derived normal erythroblasts. Human recombinant TRAIL alone variably affected the survival/growth of erythroleukemic cells; K562 cells were the most sensitive. Moreover, all erythroleukemic cells were radio-resistant, as demonstrated by the fact that cytotoxicity was evident only after treatment with high-dose (15 Gy) IR. Remarkably, when IR and TRAIL were used in combination, an additive effect was noticed in all erythroleukemic cells. Augmentation of TRAIL-induced cell death by IR was observed with both low and high IR doses and required the sequential treatment of IR 3 to 6 hours before the addition of TRAIL. Conversely, both TRAIL and IR showed a moderate cytotoxicity on primary CD34(+)-derived normal erythroblasts when used alone, but their combination did not show any additive effect. Moreover, the cytotoxicity of IR plus TRAIL observed in erythroleukemic cells was accompanied by the selective up-regulation of the surface expression of TRAIL-R1 (DR4), and it was completely blocked by the z-Val-Ala-Asp (OMe)-CH(2) (z-VAD-fmk) caspase inhibitor. On the other hand, the surface expression of TRAIL-R1 in CD34(+)-derived normal erythroblasts was unaffected by IR, which induced the up-regulation of the decoy TRAIL-R3. These data demonstrate that treatment with IR provides an approach to selectively sensitize erythroleukemic cells, but not normal erythroblasts, to TRAIL-induced apoptosis through the functional up-regulation of TRAIL-R1.     

Interleukin-4 and interleukin-5 map to human chromosome 5 in a region encoding growth factors and receptors and are deleted in myeloid leukemias with a del(5q)

Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL- 3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).     

Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor

To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.     

A new monoclonal antibody (CH-F42) recognizes a CD7- subset of normal T lymphocytes and circulating malignant cells in adult T-cell lymphoma-leukemia and Sézary syndrome.

We describe a new rat immunoglobulin M monoclonal antibody (CH-F42) that recognizes a subset (1.5% to 8%) of normal peripheral blood T lymphocytes. The phenotype of these cells was determined, using dual-color immunofluorescence, to be CD2+, CD3+, CD4+, CD5+, CD7-, CD8-. They do not express T-cell activation markers, and are positive for UCHL1 (CD45RO), but negative for 2H4 (CD45RA). The antigen was expressed on circulating malignant cells in Sézary syndrome (four of four cases) and adult T-cell lymphoma-leukemia (ATLL) (four of six cases) and negative in a variety of other hematologic malignancies tested. These included chronic and acute lymphoid leukemias of B and T lineage, together with chronic and acute myeloid leukemias. However, normal CH-F42+ cells do not display any of the ultrastructural features associated with Sézary or ATLL cells. The marked similarities between these conditions together with the shared expression of an otherwise very restricted surface antigen (CH-F42) provide strong evidence for the existence of a common normal counterpart. Preliminary characterization studies of the antigen, which is also expressed by K562 and Jurkat cells, suggest the CH-F42 antigen is an O-linked, sialated glycan on a glycoprotein.