Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; <Emphasis Type="Italic">DR</Emphasis> ainage vs. (direct) <Emphasis Type="Italic">OP</Emphasis> eration (DROP-trial)

Background

Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life.

Methods/design

Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8).

Discussion

The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor.

     

Reconstruction of a congenitally absent flexor pollicis longus in an adult

Congenital absence of the flexor pollicis longus (FPL) is an unusual finding that is frequently associated with thumb hypoplasia. Isolated FPL absence is the rarest of the congenital thumb anomalies. The present article describes a patient with a congenitally absent FPL, and discusses the chosen method of reconstruction.     

Danaparoid sodium attenuates the increase in inflammatory cytokines and preserves organ function in endotoxemic rats

Introduction  

Anticoagulant therapy attracts much attention for the treatment of severe sepsis since recent studies have revealed that some anticoagulants have the ability to regulate the inflammatory response. The purpose of this study was to examine whether danaparoid sodium (DA) is effective for the treatment of organ dysfunction in sepsis.     

Conversion to sirolimus in pediatric renal transplant patients: a single-center experience

We studied efficacy and safety of conversion from CNI- to SRL-based immunosuppression in 92 kidney TX recipients, mainly due to CAN (69%). Median time of conversion was 31 months (r: 0.3-165); median time of follow-up: 36 months (r: 2-102). In the whole group mean eGFR increased from 53 ± 22 to 67 ± 26mL/min/1.73 m(2) at three months (p = 0.02) and did not change subsequently. Patients with grade I CAN had higher eGFR than those with grade II CAN. Patient and graft survival was 96% and 70% 10 yr after conversion. Patients with grade I CAN had better graft survival than those with grade II CAN: 89% vs. 65% at six yr (p = 0.02) post conversion. There were two episodes of BPAR. Baseline proteinuria >20 mg/kg/day (HR: 10) and baseline eGFR <50 mL/min/1.73 m(2) (HR: 8) were independent predictors of graft loss. Sixty-seven of 92 subjects had ≥1 AEs: diarrhea (n = 52), urinary tract infections (n = 35), and lower respiratory tract infections (n = 12) were the most frequent. Patients with >2 AEs had SRL blood levels >9 ng/mL at month 3 (p = 0.01). In conclusion, patients converted from CNI to SRL had good graft survival and tolerable but frequent AEs. Independent predictors of graft loss were baseline proteinuria and eGFR.     

Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis [published erratum appears in Blood 1994 Nov 1;84(9):3252]

Fc gamma RIIA in the absence of other Fc receptors or receptor subunits induces the ingestion of IgG-coated cells. The cytoplasmic domain of Fc gamma RIIA contains two Y-x-x-L sequences similar to those in other Ig gene family receptors plus an additional tyrosine residue not in a Y-x- x-L motif. Upon cross-linking, Fc gamma RIIA is phosphorylated on tyrosine and the cytoplasmic tyrosines, Y275 (Y1), Y282 (Y2), and Y298 (Y3), may be important for its phagocytic activity. Because COS-1 cells can serve as a model for examining molecular structures involved in phagocytosis, substitutions and deletions were introduced into the cytoplasmic domain of Fc gamma RIIA and examined in COS-1 cell transfectants for their effects on phagocytosis and tyrosine phosphorylation. Disruption of a single cytoplasmic Y-x-x-L motif by substitution of tyrosine Y2 or Y3 by phenylalanine or by removing the threonine and leucine residues within the motif inhibited phagocytosis 50% to 65%. Tyrosine phosphorylation of Fc gamma RIIA also was inhibited, although to a greater extent by the substitution of Y3 than of Y2. Replacement of the N-terminal first cytoplasmic domain tyrosine, Y1, which is not within a typical Y-x-x-L, by itself did not inhibit phagocytosis, but replacement of Y1 in mutants lacking Y2 or Y3 virtually eliminated phagocytic activity and receptor tyrosine phosphorylation. Thus, at least two cytoplasmic tyrosines, including at least one typical single Y-x-x-L motif, are required for phagocytosis by Fc gamma RIIA. The data suggest that there is a close but not a simple relationship between phosphorylation of the Fc gamma RIIA cytoplasmic tyrosines and Fc gamma RIIA-mediated phagocytosis. Y3 appears to be particularly important because its removal by truncation or replacement with phenylalanine inhibits both tyrosine phosphorylation and phagocytosis in parallel. Alterations in the 12 residue proline-containing sequence between the two Y-x-x-L motifs also reduced phagocytic activity and tyrosine phosphorylation. Thus, the specific structure of the Fc gamma RIIA cytoplasmic domain accounts for its ability to stimulate phagocytosis in the absence of other subunits.     

Chromosome marker evidence for the bipotentiality of BFU-E

When mouse bone marrow cells are seeded in agar cultures containing erythropoietin or pokeweed mitogen stimulated spleen cell conditioned medium plus erythropoietin, megakaryocytes are found mixed with erythroid cells in approximately 40% of the erythropoietic bursts that develop in the cultures. Chromosome spreads of C-metaphases in such "megaerythro bursts" were prepared and stained in situ with a modification of the C-banding technique. In cultures seeded with mixtures of male and female cells, metaphases from individual megaerythro bursts were shown to be either all male of all female but not both. Moreover, tetraploid C-metaphases of megakaryocytes were found to be of the same sex as diploid C-metaphases of erythroid cells in the same megaerythro burst. These results provide evidence that in the mouse, a bipotential progenitor cell exists that has the capacity to give rise to cells of both the megakaryocytic and the erythrocytic lines of differentiation.     

Effect of Hemoperfusion Using Polymyxin B-immobilized Fibers on Acute Lung Injury in a Rat Sepsis Model

Direct hemoperfusion using polymyxin B-immobilized column (PMX-DHP) is recognized as an effective treatment for septic shock. However, whether its efficacy is limited to cardiovascular dysfunction remains unknown. Therefore, we planned to examine the effects of PMX-DHP in an acute lung injury model. [Materials and methods] Rats were assigned to either PMX-DHP group or control group (n= 7 in each). A lung injury was created by the intratracheal instillation of LPS. In PMX-DHP group, an arteriovenous extracorporeal circuit using PMX column was applied for three hours. The same procedure using a dummy column was applied in control group. The lung microcirculation was observed, and adherent leukocytes, RBC velocity, and the arterial PaO2 were calculated. Pathological changes and the wet/dry weight ratio of the lungs were examined. [Results] Adherent leukocytes and platelets to the lung venules were recognized at 3 hours, and their numbers increased over time. Treatment with PMX-DHP significantly suppressed these events and helped maintenance of the blood flow and PaO₂ levels. The lung edema and the histologic damages were also suppressed. [Conclusions] PMX-DHP improved the microcirculation by suppressing leukocyte and platelet adhesion. PMX-DHP had beneficial effects in a model for acute lung injury.     

Internalization and cytotoxicity analysis of silicon-based microparticles in macrophages and embryos

Microchips can be fabricated, using semiconductor technologies, at microscopic level to be introduced into living cells for monitoring of intracellular parameters at a single cell level. As a first step towards intracellular chips development, silicon and polysilicon microparticles of controlled shape and dimensions were fabricated and introduced into human macrophages and mouse embryos by phagocytosis and microinjection, respectively. Microparticles showed to be non-cytotoxic for macrophages and were found to be localized mainly inside early endosomes, in tight association with endosomal membrane, and more rarely in acidic compartments. Embryos with microinjected microparticles developed normally to the blastocyst stage, confirming the non-cytotoxic effect of the particles. In view of these results silicon and polysilicon microparticles can serve as the frame for future intracellular chips development and this technology opens the possibility of real complex devices to be used as sensors or actuators inside living cells.