Pancreaticomediastinal fistula as a rare cause of recurrent pleural effusions

A 45-year-old male with chronic alcoholism was transferred to our hospital with progressive dyspnoea, bilateral pleural effusions and ascites. Serum concentrations of lipase and CRP were increased. Pleural effusions recurred despite repeated thoracentesis, antibiotic therapy and total parenteral nutrition. A CT scan of chest and abdomen showed a lipomatous pancreas without signs of necrosis. Endosonography (EUS) demonstrated as signs of chronic pancreatitis an increased lobularity of the parenchyma without calcifications and two small cystic lesions in the pancreatic head. The pleural fluid lipase levels were markedly increased compared to a low lipase concentration in ascites. As an explanation for the pleural effusions ERCP showed a retroperitoneal fistula in the head/body region into the mediastinum and a stenosis of the pancreatic duct in the pancreatic head. For the ascites an inflammatory pathogenesis due to the exacerbation of chronic pancreatitis had to be assumed because the analysis showed an exudate with leukocytosis. After papillotomy via the pancreatic duct a 10 French wide 9 cm long stent was inserted into the pancreatic duct bridging the pancreatic fistula. Within 10 days pleural effusions had completely receded. After three weeks pancreaticography showed a total regression of the fistula and the stent was exchanged. After 6 weeks the pancreatic stent was removed with a lasting remission of the pleural effusions.     

MR imaging of therapy-induced changes of bone marrow

MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment.     

Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease

Currently, Pubmed lists 385 marker genes for neuroblastoma outcome. Using a customized neuroblastoma-microarray, we evaluated the prognostic impact of the gene-expression pattern of 349 of these candidates (90.6%) in 127 neuroblastoma patients with divergent outcome. By significance analysis of microarrays (SAM) and both uncorrected and Bonferroni-corrected ANOVA, 166/349 (47.5%), 218/349 (62.5%) and 128/349 (36.4%) candidates showed significant differential expression between patients with contrasting outcome. By Prediction Analysis for Microarrays (PAM), a 38-gene-classifier was derived from all markers, which classified patients outcome with an overall accuracy of 78.5%. However, patients with unfavorable outcome of MYCN non-amplified disease were largely misclassified (accuracy: 35%), suggesting that these courses are not identified by current marker genes.     

The potential of bioartificial tissues in oncology research and treatment

This review article addresses the relevance and potential of bioartificial tissues in oncologic research and therapy and reconstructive oncologic surgery. In order to translate the findings from basic cellular research into clinical applications, cell-based models need to recapitulate both the 3D organization and multicellular complexity of an organ but at the same time accommodate systematic experimental intervention. Here, tissue engineering, the generation of human tissues and organs in vitro, provides new perspectives for basic and applied research by offering 3D tissue cultures resolving fundamental obstacles encountered in currently applied 2D and 3D cell culture systems. Tissue engineering has already been applied to create replacement structures for reconstructive surgery. Applied in vitro, these complex multicellular 3D tissue cultures mimic the microenvironment of human tissues. In contrast to the currently available cell culture systems providing only limited insight into the complex interactions in tissue differentiation, carcinogenesis, angiogenesis and the stromal reaction, the more realistic (micro)environment afforded by the bioartificial tissuespecific 3D test systems may accelerate the progress in design and development of cancer therapies.     

Successful treatment of refractory donor lymphocyte infusion‐induced immune‐mediated pancytopenia with rituximab

A 6‐year‐old male with chronic granulomatous disease, who was transplanted with bone marrow and exhibited increasing mixed chimerism, subsequently received two donor lymphocyte infusions (DLI). Two weeks after the second DLI, the patient developed acute graft‐versus‐host disease (GVHD) and progressive pancytopenia that was associated with autoantibody production. Conventional treatment did not improve the pancytopenia. However, administration of Rituximab (RTX) (375 mg/m²/week for four consecutive weeks) resulted in a rapid resolution of the pancytopenia. The patient achieved full donor chimerism without GVHD symptoms. RTX can be valuable for managing immune‐mediated cytopenias that arise after DLI and are refractory to conventional therapies. Pediatr Blood Cancer 2010;54:329–331. © 2009 Wiley‐Liss, Inc.     

CFTR-dependent susceptibility of the cystic fibrosis-host to Pseudomonas aeruginosa

Cystic fibrosis is the most common autosomal recessive disorder in western countries. The disease is characterized by recurrent and chronic infections of the lung in particular with Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia, and Haemophilus influenzae. Albeit intensive research in the last years, the molecular mechanisms causing the high susceptibility of cystic fibrosis patients to bacterial infections are still unknown. Animal models provided important novel information on the pathophysiology of cystic fibrosis and mimicked many of the pathological findings in humans, for instance chronic inflammation and increased infection susceptibility. These animal models were recently employed to identify several proteins and lipids that are critically involved in the pathophysiology of cystic fibrosis. Thus, several studies identified death receptors, caveolin proteins, membrane rafts, and alterations of the ceramide metabolism with an accumulation of ceramide in cystic fibrosis lungs to be critically involved in the infection susceptibility, the chronic inflammation, and the reduced mucociliary clearance in cystic fibrosis.     

Intrapulmonary application of a 5-lipoxygenase inhibitor using surfactant as a carrier reduces lung edema in a piglet model of airway lavage

Leukotriene-generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar-capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5-lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurftrade mark) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air-bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B(4) (LTB(4)) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO(2)) (S, 13.8 +/- 4.2 kPa, vs. S + MK, 20 +/- 6.6; P < 0.05), functional residual capacity (S, 15.1 +/- 6.8 ml/kg, vs. S + MK, 18.8 +/- 3.7 ml/kg; P < 0.05), and EVLW (S, 29 +/- 14 ml/kg, vs. S + MK 24 +/- 4 ml/kg; P < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB(4) concentration in BAL (S, 3.5 (1.9-5.4) pg/ml, vs. S + MK, 1.6 (0.7-4.7) pg/ml; P < 0.05) and an increase in IL-8 (S, 2,103 (852-4,243) pg/ml, vs. S + MK, 3,815 (940-26,187) pg/ml; P < 0.05). PMNL counts in BAL were reduced (S, 570 +/- 42 cells/ml, vs. 275 +/- 35 cells/ml; P < 0.05). In conclusion, intrapulmonary application of the 5-lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB(4) reduction.