Survival data for 299 patients with primary cutaneous lymphomas: a monocentre study.

The aim of this study was retrospectively to assess the validity of the 2005 WHO-EORTC classification for primary cutaneous lymphomas (PCL) in a large cohort of patients of a single German skin cancer unit. All patients with PCLs consecutively visiting our hospital between January 1980 and December 2005 were included in a retrospective monocentre study, analysing their histological and clinical data. A total of 312 patients fulfilled the inclusion criteria for PCL. In 299 patients clinical information and paraffin material were sufficient for detailed classification. Of the 299 patients, 63% expressed a T-cell and 37% a B-cell phenotype. Mycosis fungoides was the entity with the highest frequency (30.9%), followed by primary cutaneous follicle centre lymphomas (16.9%) and lymphomatoid papulosis (15.9%). The mean follow-up period was 38.4 months. Five-year disease-specific survival was 80.5% for mycosis fungoides, 92.5% in primary cutaneous anaplastic large cell lymphoma, 100% in lymphomatoid papulosis, 98.1% in primary cutaneous follicle center lymphoma, 100% in primary cutaneous marginal zone lymphoma and 63.2% in diffuse large B-cell lymphoma, leg type. Our data are in line with the data collected by the WHO-EORTC. This is further evidence for the reliability of the WHO-EORTC classification and staging system.

Proliferation of rat molar pulp cells after direct pulp capping with dentine adhesive and calcium hydroxide.

The aim was to evaluate the proliferation of pulp cells 1, 3 and 7 days after direct pulp capping with the dentine adhesive Gluma Comfort Bond (GCB) and to compare it with calcium hydroxide (Ca(OH)(2)). An occlusal cavity was prepared in 72 molar teeth of 36 Wistar rats. Then GCB or Ca(OH)(2) was placed on the exposed pulp. All cavities were restored with composite. After 1, 3 and 7 days, the animals were sacrificed. One hour prior sacrification, 5-bromo-2'-desoxyuridine (BrdU) was injected into the intraperitoneal cavity for immunohistological analysis of 18 animals. BrdU was incorporated into the DNA to tag proliferating cells using an antibody staining. Three animals served as controls and were not further treated. The number of the tagged cells was statistically analysed by comparing the results of the three groups. In 18 rats, routine histological analysis was performed in order to evaluate the pulp tissue for bacterial infection, inflammatory cells and necrosis. The marked cells were identified as fibroblasts, endothelial cells (after 1, 3 and 7 days) and Höhl cells (after 7 days). One day after capping, significantly more cells were stained in the GCB than in the Ca(OH)(2) group (p < 0.05). After 3 days, significantly more cells were stained in the GCB than in the Ca(OH)(2) and the control group (p < 0.016). Direct contact of GCB with pulp tissue leads to an increased formation of granulation tissue (fibroblasts, endothelial cells) because of an inflammatory reaction. This may be explained by missing antibacterial effect and foreign body reactions. Also, GCB may have a negative effect on Höhl cells.

New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas.

BACKGROUND: There is a growing body of literature that has enhanced our understanding of the biology of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) including in the context of gene profiling studies. Recent studies have demonstrated an activated proliferation profile associated with leg type lymphoma including overexpression of proto-oncogenes PIM1, PIM2, and cMYC, and the transcription factors MUM1 and OCT2. Although gene profiling is very useful in understanding the molecular basis of diffuse large B-cell lymphoma (LBCL), it is not practical from a routine diagnostic perspective. In this regard, the purpose of the study was to further define an armamentarium of easily applied immunohistochemical stains to accurately prognosticate PCDLBCL. METHODS: In all, 35 patients with PCDLBCL, 14 of follicle center and 21 of leg type, were analyzed using antibodies against CD5, CD138, BCL2, BCL6, OCT2, MUM1, FOXP1, and cMYC. Findings were correlated with clinical data. RESULTS: All cases stained negative for CD5 and CD138. Both subtypes differed in distinct staining patterns for BCL6, BCL2, OCT2, MUM1, and FOXP1. Staining for BCL2, OCT2, and/or MUM1 was associated with poor, and BCL6 with a favorable prognosis. Expression of cMYC was irrespective of prognosis or subtype, whereas ulceration or primary manifestation on the leg or multiple lesions was indicative for worse prognosis. LIMITATIONS: Case number was a limitation. CONCLUSION: Discriminating PCDLBCL supports the validity of the World Health Organization/European Organization for Research and Treatment of Cancer classification. To identify risk factors in patients with PCDLBCL we recommend thorough evaluation of clinical presentation and exploratory staining pattern for BCL2, BCL6, MUM1 and OCT2.

A histologic investigation of direct pulp capping in rodents with dentin adhesives and calcium hydroxide.

OBJECTIVE: To investigate reactions of pulp tissue when in contact with the dentin adhesives Resulcin AquaPrime + MonoBond (RAPMB, Merz Dental), Scotchbond 1 (SB1, 3M ESPE), and Gluma Comfort Bond (GCB, Heraeus Kulzer) in comparison with calcium hydroxide after 1 to 70 days. METHOD AND MATERIALS: An occlusal cavity was prepared in 152 molars of 76 Wistar rats. The pulps were exposed and dentin adhesives placed on the pulp tissue of 10 molars for each dentin adhesive group and time period. Eight molars per time period served as controls and were capped with calcium hydroxide. All cavities were restored with composite resin. The animals were sacrificed 1, 3, 7, and 70 days after pulp capping. Pulp tissue was histologically evaluated for the following criteria: bacterial infection, inflammatory cells, necrosis, and reparative dentin. The data were statistically evaluated using the Kruskal-Wallis test (P < .05). RESULTS: Overall, significantly more bacterial infections were detected 1, 3, 7, and 70 days after pulp capping with dentin adhesive (P < .05). In all dentin adhesive groups, 1 day after direct pulp capping, significantly more inflammatory cells were found, whereas after 7 days, this was only the case for the SB1 group (P < .05). After 70 days, capping with calcium hydroxide resulted in significantly less necrosis than with RAPMB and SB1 (P < .05). Regarding necrosis, SB1 showed the worst results: Pulp necrosis occurred significantly more often than with calcium hydroxide and GCB (P < .05). After the application of calcium hydroxide, significantly more reparative dentin formation occurred (P < .05). CONCLUSION: Direct pulp capping with calcium hydroxide seems to produce remarkably better results than with dentin adhesive.

Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy.

BACKGROUND: Generalized arterial calcification of infancy has been reported to be frequently lethal, and the efficiency of any therapy, including bisphosphonates, is unknown. A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy. METHODS AND RESULTS: We performed a multicenter genetic study and retrospective observational analysis of 55 subjects affected by generalized arterial calcification of infancy to identify prognostic factors. Nineteen (34%) patients survived the critical period of infancy. In all 8 surviving patients tested, hypophosphatemia due to reduced renal tubular phosphate reabsorption developed during childhood. Eleven of 17 (65%) patients treated with bisphosphonates survived. Of 26 patients who survived their first day of life and were not treated with bisphosphonates only 8 (31%) patients survived beyond infancy. Forty different homozygous or compound heterozygous mutations, including 16 novel mutations in ENPP1, were found in 41 (75%) of the 55 patients. Twenty-nine (71%) of these 41 patients died in infancy (median, 30 days). Seven of the 14 (50%) patients without ENPP1 mutations died in infancy (median, 9 days). When present on both alleles, the mutation p.P305T was associated with death in infancy in all 5 cases; otherwise, no clear genotype-phenotype correlation was seen. CONCLUSION: ENPP1 coding region mutations are associated with generalized arterial calcification of infancy in approximately 75% of subjects. Except for the p.P305T mutation, which was universally lethal when present on both alleles, the identified ENPP1 mutations per se have no discernable effect on survival. However, survival seems to be associated with hypophosphatemia linked with hyperphosphaturia and also with bisphosphonate treatment.

The influence of blood group differences in allogeneic hematopoietic peripheral blood progenitor cell transplantation.

BACKGROUND: Severe immunohematologic complications after ABO-mismatched allogeneic blood peripheral blood progenitor cell (PBPC) transplantation (PBPCT), including pure red cell aplasia and immune hemolysis, have been described. Although several studies have addressed this issue, the clinical influence of blood group differences on transfusion requirements and survival is still discussed controversially, especially in the case of PBPCT. STUDY DESIGN AND METHODS: This single-center study is based on 143 patients receiving PBPCT after standard or reduced-intensity conditioning. The influence of blood group differences in the ABO, Rh, and Kell systems on red blood cell, platelet, and plasma transfusion requirements; length of hospitalization in transplantation unit; survival; and occurrence of graft-versus-host disease was investigated. Additionally, the influence of the conditioning regimen and irregular antibodies on the measures mentioned above was analyzed. RESULTS: Multivariate analysis demonstrated that minor and bidirectional ABO mismatch (p = 0.028) and Rh difference (p = 0.020) independently led to poorer survival. The Kell difference did not show significant influences on the measures mentioned above. A clinically relevant influence of blood group differences on transfusion requirements could not be demonstrated. Irregular antibodies also did not show significant influences. CONCLUSION: These findings indicate an influence of blood group differences in PBPCT on survival and must be studied in further detail.

Cryopreservation reduces the concentration of detectable bacteria in contaminated peripheral blood progenitor cell products.

BACKGROUND: Microbial contamination of PBPC products PBPCPs may cause severe clinical complications. There-fore, we investigated the influence of cryopreservation on the sensitivity to detect bacterial contaminations in PBPCPs. STUDY DESIGN AND METHODS: Expired PBPCPs (n = 29) were thawed, and defined concentrations of Staphylococcus epidermidis or Escherichia coli were inoculated into each bag. After 60 minutes of intermixing, a representative aliquot was drawn and cultured on Mueller-Hinton agar for 24 hours. Then, the products were cryopreserved for 24 hours, and the procedure was repeated as mentioned above. The total numbers of CFUs were counted before and after cryopreservation. RESULTS: A mean concentration of 2529 CFUs per mL of S. epidermidis was determined before cryopreservation versus 2182 CFUs per mL after cryopreservation, demonstrating a decrease of detectable colonies (p < 0.05). For E. coli, the mean numbers were 424 CFUs per mL before cryopreservation and 343 CFUs per mL after cryopreservation, also showing a decrease (p < 0.05). CONCLUSION: The cryopreservation reduces the concentration of detectable bacteria in contaminated PBPCPs. Especially in sterility testing of PBPCPs with low bacterial contamination, this phenomenon could lead to false-negative results with severe clinical consequences.

Factors affecting the efficacy of peripheral blood progenitor cells collections by large-volume leukaphereses with standardized processing volumes.

BACKGROUND: Peripheral blood progenitor cell (PBPC) collections should be safe and efficient. Therefore, the influence and risk factors in large-volume leukaphereses (LVL) with standardized blood volumes was investigated. STUDY DESIGN AND METHODS: In a total of 724 autologous LVL performed at our center, either 4x or 6x the patient's blood volume (PBV) was processed. The group with processing 4x the PBV showed a median of 31 circulating CD34+ cells per microL, and the group with processing 6x the PBV had a median of 13 CD34+ cells per microL before LVL. Individual clinical factors, laboratory factors, and apheresis run variables influencing the yields of PBPCs were retrospectively analyzed. Furthermore, the changes of laboratory variables and adverse effects during LVL were investigated. RESULTS: Multivariate analysis identified "age,""circulating CD34+ cells," and "percentage of mononuclear cells" as only factors influencing the yields of PBPCs. Altogether, processing 6x versus 4x the PBV did not result in significantly higher yields of CD34+ cells for the total group, but requested PBPC yields were achieved more often after processing 6x the PBV in patients below 20 CD34+ cells per microL blood. Processing 6x versus 4x the PBV showed a significant difference for the decrease of platelets, but not for any other laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without accumulation in one group. CONCLUSION: In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.

Processing of peripheral blood progenitor cell components in improved clean areas does not reduce the rate of microbial contamination.

BACKGROUND: Microbial contamination of peripheral blood progenitor cell components (PBPCs) may cause severe complications in immunosuppressed recipients. Therefore, principles of Good Manufacturing Practice (GMP) are applicable for processing of PBPC components to reduce potential risks of contamination. STUDY DESIGN AND METHODS: It was investigated in a retrospective study whether the microbial contamination of PBPC components could be reduced after processing in improved clean areas according to the "Manufacture of Sterile Medicinal Products." Starting in 1994, a total of 1478 autologous and allogeneic PBPC components have been collected and processed into 3149 cryopreservation bags at the Department of Transfusion Medicine. Sterility testing was performed for all bags. Until December 1998, 783 PBPC components were processed at a clean bench only (group I). Thereafter, 695 PBPC components have been processed at a clean bench located in a clean area with an airlock system for personnel and equipment (group II). RESULTS: In group I, 16 of 1555 bags (1.03%) showed positive results in the first sterility testing. In group II, 21 of 1594 bags (1.32%) were positive (p = NS). The clinical follow-up was inconspicuous. CONCLUSION: Microbial contamination of PBPC components could not be reduced by installation of improved clean area conditions.

Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial.

BACKGROUND: External cardioversion is a readily available treatment for persistent atrial fibrillation. Although anatomical and electrophysiological considerations suggest that an anterior-posterior electrode position should create a more homogeneous shock-field gradient throughout the atria than an anterior-lateral position, both electrode positions are equally recommended for external cardioversion in current guidelines. We undertook a randomised trial comparing the two positions with the endpoint of successful cardioversion. METHODS: 108 consecutive patients (mean age 60 years [SD 16]) with persistent atrial fibrillation (median duration 5 months, range 0.1-120) underwent elective external cardioversion by a standardised step-up protocol with increasing shock strengths (50-360 J). Electrode positions were randomly assigned as anterior-lateral or anterior-posterior. If sinus rhythm was not achieved with 360 J energy, a single cross-over shock (360 J) was applied with the other electrode configuration. A planned interim analysis was done after these patients had been recruited; it was by intention to treat. FINDINGS: Cardioversion was successful in a higher proportion of the anterior-posterior than the anterior-lateral group (50 of 52 [96%] vs 44 of 56 [78%], difference 23.7% (95% CI 9.1-37.8, p=0.009). Cross-over from the anterior-lateral to the anterior-posterior electrode position was successful in eight of 12 patients, whereas cross-over in the other direction was not successful (two patients). After cross-over, cardioversion was successful in 102 of 108 randomised patients (94%). INTERPRETATION: An anterior-posterior electrode position is more effective than the anterior-lateral position for external cardioversion of persistent atrial fibrillation. These results should be considered in clinical practice, for the design of defibrillation electrode pads, and when guidelines for cardioversion of atrial fibrillation are updated.