Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 73 records · Page 4Linked to original sources

PubMed2000

Vascularization of head and neck paragangliomas: comparison of three MR angiographic techniques with digital subtraction angiography.

BACKGROUND AND PURPOSE: MR angiography of the head and neck region has been studied widely, but few studies have been performed concerning the efficacy of MR angiography for the identification of the specific vascular supply of the highly vascular head and neck paragangliomas. In this study, we compared three MR angiography techniques with respect to visualization of branch arteries in the neck and identification of tumor feeders in patients with paragangliomas. METHODS: Fourteen patients with 29 paragangliomas were examined at 1.5 T using 3D phase-contrast (PC), 2D time-of-flight (2D TOF), and multi-slab 3D TOF MR angiography. In the first part of the study, two radiologists independently evaluated the visibility of first-, second-, and third-order branch arteries in the neck. In the second part of the study, the number of feeding arteries for every paraganglioma was determined and compared with digital subtraction angiography (DSA), the standard of reference in this study. RESULTS: Three-dimensional TOF angiography was superior to the other MR angiography techniques studied (P < .05) for depicting branch arteries of the external carotid artery in the neck, but only first- and second-order vessels were reliably shown. DSA showed a total of 78 feeding arteries in the group of patients with 29 paragangliomas, which was superior to what was revealed by all MR angiography techniques studied. More tumor feeders were identified with 3D TOF and 2D TOF angiography than with 3D PC MR angiography (P < .05), with a sensitivity/specificity of 61%/98%, 54%/95%, and 31%/95%, respectively. Sensitivity was lowest for carotid body tumors. CONCLUSION: Compared with intra-arterial DSA, the 3D TOF MR angiography technique was superior to 3D PC and 2D TOF MR angiography for identifying the first- and second-order vessels in the neck. With 3D TOF angiography, more tumor feeders were identified than with the other MR angiography techniques studied. The sensitivity of MR angiography, however, is not high enough to reveal important vascularization. The sensitivity of MR angiography is too low to replace DSA, especially in the presence of carotid body tumors.

Adult↗

PubMed2000

[++Scintimammography: a new imaging technique for diagnosis and follow-up of breast cancer].

99m Tc MiBi has emerged as a new imaging technique for primary breast carcinomas. The aim of this study was to analyze the diagnostic performance and the additional information provided by scintimammography (SMN). Two hundred and forty consecutive women referred to surgery for abnormalities breast or suspicious breast cancer were scanned before surgery. Sensitivity and specificity were respectively 92% and 53%. PPV: 77.5% and PVN: 79.3%. All false negative scans occurred in cancers 1 cm. SMN detected multiple foci of uptake in the same breast in 13%, that were all confirmed to be multifocal disease and histology. Controlateral focal uptake was also detected; at this time 5/27 are confirmed to be bilateral breast neoplasms; 22 patients are in follow-up. SMN is reliable in the diagnosis of breast cancer and also with difficult cases of mammography. Moreover, SMN provides additional qualitative information in 19.6% of breast carcinomas, such as chest wall infiltration, multifocal or bilateral breast cancer.

Adenocarcinoma, Mucinous↗

PubMed1999

The "random-coil" state of proteins: comparison of database statistics and molecular simulations.

This study presents a comparison of two models of the random-coil state, one based on statistical distributions from the structural database and the other based on molecular dynamics simulations. The database model relies on the assumption that the random- or statistical-coil state of a particular residue can be described by its conformational distribution in a sufficiently diverse subset of protein structures. The molecular dynamics model is based on distributions from molecular simulations carried out on "dipeptide" models (single residues with N-terminal acetyl and C-terminal N'-methyl amide blocking groups). A comparison of the two models for the residues Ala, Asn, Asp, Gly, and Val indicates that the database distributions are greatly influenced by long-range interactions and dominated by specific recognizable elements of protein structure. In contrast, the limited structural scope of the dipeptide models presents the extreme case of a peptide under the influence of only short-range interactions. The models were evaluated by a comparison of scalar coupling constants calculated from the conformational distributions and compared with experimentally values determined for unstructured peptides. Although the models gave different distributions, there was similar agreement with experiment. This comparison emphasizes the differences and limitations in each model and highlights the difficulty in presenting an accurate picture of the random-coil state. Proteins 1999;36:407- 418.

Computer Simulation↗

PubMed1999

Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991).

In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et al, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on leukemia cell mass and response to initial treatment: standard-risk group (SRG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a randomized study on late intensification (protocol S) was performed in RG patients, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65. 3% (standard error [SE] 3.2%), which was significantly different from the 73% (SE 1%) 5-year EFS achieved in the ALL-BFM-86 study (P =.02, Z-test). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates were 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant difference could be established (P =.67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12.0%), respectively. SRG patients receiving protocol II fared better than patients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54. 5% [SE 7.5], respectively). No difference in 5-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CNS relapses occurred in SRG patients receiving protocol II. Six children died in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective method of CNS prophylaxis in the context of BFM-oriented treatment for all children with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DCLSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early reinduction with protocol II is essential in the treatment of SRG patients and that late intensification with protocol S does not improve the prognosis for RG patients.

Adolescent↗

PubMed1999

HLA-B8 and HLA-A3 coexpressed with HLA-B8 are associated with a reduced risk of the development of chronic myeloid leukemia. The Chronic Leukemia Working Party of the EBMT.

Chronic myeloid leukemia (CML) is characterized by the chromosomal translocation t(9;22) resulting in the chimeric bcr-abl oncogene that encodes the P210 fusion protein, which contains a unique amino acid sequence. If peptides derived from the leukemia-specific part of P210 are expressed in HLA molecules on the cell membrane of leukemic cells, an immunological response may occur. Recent studies using synthetic peptides identical to the bcr-abl fusion region showed that some peptides are capable of binding to HLA-A3, -A11, and -B8 molecules. Cytotoxic T-cell responses have been induced against bcr-abl-derived synthetic peptides bound to HLA-A3 and -B8. We hypothesized that if antigen processing of the P210 fusion protein leads to presentation of peptides from the fusion region by major histocompatibility complex (MHC) molecules in vivo, this may be reflected in a diminished incidence of CML in individuals expressing HLA-A3, -A11, or -B8. Consequently, lower frequencies of these antigens would be expected in patients with CML compared with unaffected individuals. A case-control study and a meta-analysis were performed to test this hypothesis. The multicenter case-control study compared patients with CML from the data base of the European Group for Blood and Marrow Transplantation (EBMT) with unaffected individuals from the registry of Bone Marrow Donors Worldwide. Patients and controls were matched per country. The meta-analysis consisted of five studies reported in the literature. The multicenter case-control study consisting of 1,899 patients and 512, 363 bone marrow donors as controls yielded odds ratios (ORs) of 0.90 (95% confidence interval [CI], 0.80 to 1.00) for HLA-A3, 1.16 (95% CI, 1.02 to 1.33) for HLA-A11, and an OR of 0.73 (95% CI, 0.65 to 0. 82) for HLA-B8. Coexpression of HLA-A3 and HLA-B8 gave an OR of 0.51 (95% CI, 0.40 to 0.67). This can be translated in a protective effect of 27% for HLA-B8, 10% for HLA-A3, and 49% protection for the combination of HLA-A3 and HLA-B8. The meta-analysis comprising 463 CML patients and 4,912 controls showed a 29% risk reduction for individuals expressing HLA-B8 (OR of 0.71; 95% CI, 0.52 to 0.97), but an OR of 1.19 (95% CI, 0.90 to 1.56) for HLA-A3 and an OR of 1. 09 (95% CI, 0.80 to 1.50) for HLA-A11. In conclusion, these results indicate that HLA-B8 expression, in particular when HLA-A3 is coexpressed, is associated with a diminished incidence of CML. A biological mechanism may be that presentation of bcr-abl breakpoint peptides in these HLA molecules can induce a protective immune response.

Case-Control Studies↗

PubMed1999

Classification of gastric carcinoma using the Goseki system provides prognostic information additional to TNM staging.

BACKGROUND: Due to the high variability of the epidemiology, genetics, morphology, and biologic behavior of gastric carcinoma, many classification systems are in use, e.g., the World Health Organization (WHO) classification; tumor differentiation; the criteria of Ming, Mulligan, and Laurén; and the recently introduced Goseki classification. In the authors' opinion, the TNM staging is the most valuable classification system, with a prognostic value for survival. METHODS: To assess the reproducibility and usefulness of these systems in clinical practice, material from 285 gastric carcinoma patients entered in the Dutch Gastric Cancer Trial was analyzed by a panel of 5 experienced gastrointestinal pathologists. The presence of eosinophilic and lymphocytic infiltrates was analyzed in addition to the TNM staging. RESULTS: Of the analyzed classification systems, only TNM stage, tumor differentiation, eosinophilic infiltrate, and the Goseki system contained information associated with the survival of patients with gastric carcinoma. The reproducibility was perfect for tumor differentiation (Kappa 1.00), nearly perfect for the WHO and Goseki classifications (Kappa 0.86 and 0.87, respectively), reasonably good for Laurén and lymphocytic infiltrate (Kappa 0.70), and reasonably good for eosinophilic infiltrate (Kappa 0.42). CONCLUSIONS: Of all these systems, the Goseki classification was the only system with prognostic value that is additional to TNM staging.

Adenocarcinoma↗

PubMed1999

Influence of abdominal-wound closure technique on complications after surgery: a randomised study.

BACKGROUND: Wound complications that occur after closure of midline laparotomy remain challenging. A new continuous double-loop closure (CDLC) technique was developed to avoid wound rupture through resistance to high intra-abdominal pressure and continued approximation of wound edges. We investigated the efficacy of this technique. METHODS: We randomly assigned 390 patients undergoing midline laparotomy-wound closure with the commonly used continuous running suture (CRS) technique (n=204) or with the CDLC technique (n=186). We assessed the influence of closure technique on the rate of wound and other complications, with emphasis on wound dehiscence, pulmonary complications, and death. FINDINGS: The rate of wound complications did not differ significantly between groups. Pulmonary complications were seen in 11 patients (5.4%) in the CRS group, and in 32 patients (17.2%) in the CDLC group (p=0.0002). In the CRS group, 17 (8.3%) patients died, compared with 39 (21.0%) patients in the CDLC group (p=0.0004). INTERPRETATION: The CDLC technique should not be used. The lessened compliance of the abdominal wall, which raises intra-abdominal pressure for long periods, may increase the risk of postoperative pulmonary complications and death. The ideal closure technique should combine strength to prevent wound rupture with elasticity to adapt to increased intra-abdominal pressure.

Aged↗

PubMed1999

Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study.

BACKGROUND: The correlation between human papillomavirus (HPV) infection and tumor prognosis in 159 Russian women with cervical carcinoma was investigated. The presence of various HPV types was correlated with the histologic parameters of the carcinomas and with their immunoreactivity with antibodies to p53, Ki-67-Ag, and bcl-2. METHODS: Formalin fixed, paraffin embedded tissue specimens representing 159 cases of International Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA was detected by polymerase chain reaction (PCR) using a general primer set that targets the L1 region and synthesizes a product of only 65 base pairs. The HPV types were determined by direct sequencing and compared with known HPV types. RESULTS: All 159 carcinomas were positive for HPV. HPV 16 (64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45 (8.2%). In 6 patients (3.8%), HPV types could not been further classified, and these cases were therefore categorized as HPV X. Although a trend was noted toward poorer prognosis for women with carcinomas harboring HPV types 16, 18, and 45 than for patients with carcinomas harboring HPV types 31, 33, 35, 52, 56, 58, and 68, the differences were not statistically significant. The prevalence of adenocarcinoma and adenosquamous carcinoma was higher among HPV 18 positive patients than among patients with the other known HPV types (P=0.0002). CONCLUSIONS: The rate of HPV positivity in these 159 cervical carcinomas was 100%. These findings challenge the assumption that HPV negative cervical carcinomas exist. This high rate might be attributed to the use of a new broad-spectrum HPV PCR test. HPV typing in cervical carcinoma was not significantly related to clinical outcome. HPV 18 was significantly more frequently found in adenocarcinoma and adenosquamous carcinoma. The possibility of classifying HPV 45 as an oncogenic high risk type should be considered.

Adult↗

PubMed1999

ES/IS: estimation of conformational free energy by combining dynamics simulations with explicit solvent with an implicit solvent continuum model.

This paper reviews a recently developed method for calculating the total conformational free energy of a solute macromolecule in water solvent. The method consists of a relatively short simulation by molecular dynamics with explicit solvent molecules (ES) to produce a set of microstates of the macroscopic conformation. Conformational internal solute energy and entropy are obtained from the simulation, the latter in the quasi-harmonic approximation by analysis of the covariance matrix. The implicit solvent (IS) surface energy-dielectric continuum model is used to calculate the average solvation free energy as the sum of the free energies of creating the solute-size hydrophobic cavity, of the van der Waals solute-solvent interactions and of the polarization of water solvent by the solute's charges. We have earlier applied this method to calculate the conformational free energy of native and intentionally misfolded globular conformations of proteins (the EMBL set of deliberately misfolded proteins), and have obtained good discrimination in favor of the native conformations in all instances. These results are summarized and further analyzed to show that, on average, three major component terms of the free energy all contribute in favor of discrimination. We discuss possible improvements of the ES/IS method. It is shown how the force field can be made self-consistent by adapting the parameters for calculation of surface and polarization free energies closely to the molecular mechanics force field used in the dynamics simulation, using established simulation methods to compute free energies for cavity formation and a charging process with the molecular mechanics force field to provide a set of (quasi-experimental) reference data that can be used to refine the parameters of the continuum models. The molecular surface area together with a microscopic surface free energy near 70 cal/(mol A2) is found to be a consistent descriptor of the cavity free energy. Preliminary results indicate that a linear-response approximation for the polarization of water solvent reaction near typical polar and charged protein groups is accurate to within approximately 90%.

Algorithms↗

PubMed1999

Extended lymph-node dissection for gastric cancer.

BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS: Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.

Aged↗

PubMed1999

MRI of liver metastases: limitation of spleen-liver model in optimizing pulse sequences.

The spleen-liver model, as a predictor for contrast-to-noise ratio (C/N) in liver metastases, was verified for seven sequences in 22 patients with 70 colorectal metastases. Optimization of conventional spin-echo, T1-magnetization-prepared gradient-echo and fat frequency-selective presaturation inversion-recovery fast spin echo can be done using the spleen-liver model. C/N of liver-spleen and liver-metastases, however, differed significantly on our T1 gradient-echo and T2-weighted fast spin-echo images, with and without fat-selective saturation.

Adult↗

PubMed1999

Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function.

OBJECTIVE: Renovascular disease may lead to ischemia of the nephrons and to fibrosis, which is generally considered to be irreversible and progressive. We investigated the potential of revascularization to recover and stabilize renal function in patients with ischemic nephropathy. METHODS: In a retrospective analysis of all our 61 patients with ischemic nephropathy who underwent treatment with surgical revascularization, we determined the long-term course of renal function decline with an estimated glomerular filtration rate (EGFR; Cockcroft and Gault formula). With the assumption of normal renal function at age 25 years, the preoperative slope of EGFR and the postoperative slope of EGFR were determined from the EGFR before surgery, at the short-term follow-up examination (on average, 8 months after surgery), and at the long-term follow-up examination (on average, at 47 months after surgery). These declines in renal function were compared with EGFR values in age-matched and sex-matched samples from a large cross-sectional population study. RESULTS: The overall surgical mortality rate amounted to 13.1%. Five patients became dialysis dependent-two with preexisting end-stage renal disease and three at later follow-up examination-and two patients, who before surgery were dialysis dependent, could be withdrawn from dialysis treatment. Shortly after the operation, the mean EGFR level had increased from 28.3 to 43.1 mL/min/1.73 m2 ( P <. 01). The rate of decline in renal function had decreased from an estimated -2.57 mL/min/1.73 m2/year before surgery (weighted mean: interquartile range, -2.71 to -1.98) to -0.66 mL/min/1.73 m2/year (weighted mean: interquartile range, -2.00 to -0.18) in the short-term interval to the long-term interval, which was even slightly better than the slope of -0.84 mL/min/1.73 m 2/year in the age-matched and sex-matched control population. CONCLUSION: Surgical revascularization in selected patients with renovascular disease and ischemic nephropathy restores renal function and makes the average long-term rate of decline in renal function equal to that of the general population. This indicates that in most patients a "point-of-no-return" has not yet been passed even though their renal function is already markedly impaired before surgery. Therefore, in well-selected patients with ischemic nephropathy, considerable improvement of renal function can be realized.

Adult↗

PubMed1999

Chemotherapy for operable gastric cancer: results of the Dutch randomised FAMTX trial. The Dutch Gastric Cancer Group (DGCG).

The aim of this trial was to investigate whether pre-operative chemotherapy leads to a 15% higher curative resectability rate in patients with operable gastric cancer. In this randomised trial, patients were allocated to receive either four courses of chemotherapy using 5-fluorouracil, doxorubicin and methotrexate (FAMTX) prior to surgery or to undergo surgery only. Patients younger than 75 years of age with a good physical and mental condition and a histologically proven adenocarcinoma of the stomach without clinical or radiographic (computed tomography scan) evidence of distant metastases were eligible for this trial. Early gastric cancer or cardia carcinoma were excluded. The response to chemotherapy was evaluated after two and four courses. In case of progressive disease (PD) after two courses, patients were operated upon as soon as possible. Otherwise complete response (CR) partial response (PR) or stable disease (SD), two more courses were scheduled. The standard surgical procedure was a limited lymphadenectomy (D1) with staging biopsy of the para-aortic lymph nodes. Between September 1993 and February 1996, 56 eligible and evaluable patients were entered: 27 were randomised to receive FAMTX before surgery and 29 to undergo surgery only. In the FAMTX + surgery treatment group, 15/27 (56%) had curative resections versus 18/29 (62%) in the surgery only arm. There was no difference in the frequency of TNM stages I + II in both treatment arms: 15/27 versus 15/29. Due to PD and/or toxicity, 12 patients (44%) could not complete the planned four courses of FAMTX. Response evaluation after chemotherapy was possible in 25 patients: 2 CR, 6 PR, 8 SD and 9 PD. The difference in curative resectability rate was 6.5% (95% confidence interval -32 to +19%) in favour of surgery only. Downstaging for stages I + II did not occur. PD was more often the reason for not completing the planned four courses than toxicity. More active regimens than FAMTX are required for future randomised trials.

Adenocarcinoma↗

PubMed1999

Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT).

Data from the annual survey on transplant activity 1997, collected from 457 transplant teams in 31 European countries by the European Group for Blood and Marrow Transplantation (EBMT) were used to describe current status and to assess relative and absolute changes in indication, donor type and stem cell source compared to 1991. A total of 16950 patients were reported to have a first blood or marrow transplant in 1997, a total of 18 923 procedures, including re- and double transplants were performed. Of the 16950 first transplants, 4751 (28%) were allogeneic, 12199 (72%) autologous transplants. Of the autologous transplants, 829 (7%) were bone marrow derived, 11370 (93%) from peripheral blood stem cells or combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 3311 (70%) were bone marrow, 1440 (30%) were peripheral blood stem cell transplants. In 1991, the respective figures were 2175 allogeneic (44%) and 2786 (56%) autologous transplants, more than 90% of the autologous, all allogeneic transplants bone marrow derived. Main indications in 1997 were leukemias with 5253 transplants (31%), 70% allogeneic; lymphomas with 6773 transplants (40%), 94% autologous; solid tumors with 4154 transplants (24%), 99% autologous; non-malignant disorders with 770 transplants (5 %), 85 % allogeneic. There was an absolute increase of 11971 transplants since 1991. An increase was observed in all disease categories. Marked differences were found, when the relative increase index (RII) for specific disease categories over time was analyzed. In allogeneic transplants, relatively more transplants were performed in 1997 for acute myeloid leukemia beyond 1st complete remission (RII 1.28), myelodysplastic syndromes (RII 1.58), chronic lymphocytic leukemia (RII 1.33) and non-Hodgkin's lymphoma (RII 1.58). For autologous transplant indications, a high relative increase index was observed in myelodysplastic syndromes (RII 3.77), in multiple myeloma (RII 2.12) and carcinoma of the breast (RII 6.37) with a relative decrease in leukemias (RII 0.39) and certain solid tumors such as glioma (RII 0.27) and neuroblastoma (RII 0.46). These data present the current status of blood and marrow transplantation in Europe. They show the change from bone marrow to blood as stem cell source and highlight shifts in indication. They provide a basis for patient counselling and health care planning.

Bone Marrow Transplantation↗

PubMed1999

The number of nucleated cells reflects the hematopoietic content of umbilical cord blood for transplantation.

A single umbilical cord blood (UCB) collection may contain sufficient hematopoietic stem cells to achieve engraftment and repopulation of the hematopoietic system of children and adults after myeloablative therapy. The hematopoietic potential of a UCB unit is often defined by the number of CD34+ cells or the number of colony-forming units as measured in semisolid hematopoietic progenitor cell (HPC) cultures. However, these assays are relatively difficult to standardize between UCB banks. The number of nucleated cells infused per kilogram body weight of the recipient is also reported to be a significant factor in the speed of recovery of neutrophils and platelets after transplantation. To analyze which parameters could be used to evaluate the hematopoietic potential of a UCB graft, we evaluated almost 300 UCB units that were collected for banking for unrelated transplantation. A strong correlation was found between the frequencies of CD34+ cells and the HPC as measured in semi-solid medium cultures. From the various leukocyte subpopulations, the concentration and total numbers of nucleated cells correlated best with both the HPC content and the number of CD34+ cells. Differentiation of these nucleated cells into subsets of leukocytes offered no advantage for better prediction of HPC or CD34+ cells. These results indicate that the nucleated cell count probably reflects the hematopoietic potential of a UCB graft, and may for that reason correlate with the speed of engraftment after transplantation.

Adult↗

PubMed1999

Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy.

Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases. Furthermore, its exact relation to primary diffuse large B cell lymphoma (DLBCL) of the stomach is not clear. We applied in situ hybridisation (ISH) with centromeric probes on 43 samples of 39 patients with primary gastric lymphoma (13 samples with low-grade MALT lymphoma, 25 with high-grade MALT lymphoma and five with DLBCL) to detect numerical aberrations of 10 chromosomes. ISH was performed immunohistochemically on nuclei isolated from paraffin-embedded resection tissue and on whole paraffin sections using immunofluorescence. In six of 13 low-grade MALT lymphomas trisomy was detected (46%) and mostly involved chromosome 3 (33%). In high-grade MALT lymphomas, trisomies were found in 16 of 25 cases (64%), mainly involving chromosomes 12 and 18. Trisomy 3 was present in only 13% of these cases. Of five DLBCL, only one showed trisomy. Nine of the 16 aberrant high-grade MALT lymphomas (56%) showed trisomy of more than one chromosome per case vs two of six for low-grade cases. In lymphomas with separate low- and high-grade tumour components some trisomies were detected in both components, whereas others occurred only in the high-grade tumour cells. This supports the hypothesis that high-grade MALT lymphomas can develop from a low-grade type and that this progression is accompanied by the acquisition of more genetic aberrations. However, trisomy 3 probably does not play a major role in this progression.

Chromosomes, Human, Pair 3↗

PubMed1999

CD44 expression predicts disease outcome in localized large B cell lymphoma.

Diffuse large B cell non-Hodgkin's lymphomas (DLCL) form a heterogeneous group of tumors with diverse morphology, clinical features, treatment response and prognosis. The biological variables underlying this heterogeneity are unknown. In the present study, we explored the value of the lymphocyte homing receptor CD44, a putative determinant of lymphoma dissemination, in predicting prognosis in DLCL. Expression of the standard form of CD44 (CD44s) and of CD44 isoforms containing exon v6 (CD44v6) on tumor cells was assessed by immunohistochemistry in a cohort of 276 DLCL patients from a population based lymphoma registry. We observed that CD44s as well as CD44v6 expression correlated with tumor dissemination in patients with primary nodal DLCL. Importantly, in patients with localized nodal disease, CD44s was a strong prognosticator predicting tumor related death independent of the other parameters of the International Prognostic Index (IPI). Incorporation of CD44s in the IPI parameter 'stage', increased the prognostic value of this parameter in nodal DLCL. Our data identify CD44 as a biological prognosticator, which can be used to 'fine-tune' the IPI for nodal DLCL.

Adult↗

PubMed1999

Primary non-Hodgkin's lymphoma of bone: a clinicopathological investigation of 60 cases.

A retrospective analysis of patients presenting with primary lymphoma of bone (PLB) was performed to determine clinical factors affecting prognosis in relation to histological subtype and treatment outcome. Data from 106 patients, presenting with a PLB between 1943 and 1996, were retrieved from the files of the Netherlands Committee on Bone Tumours and Leiden University Medical Centre. The lymphomas were reclassified according to the REAL and updated Kiel classification. The clinical presentation, survival and prognostic factors were investigated. Sixty patients had sufficient clinical information and adequate follow-up to be included in the study. All 33 PLB that could be immunophenotyped were of B cell origin. According to the REAL classification, most PLB were large (B) cell lymphomas (92%) and according to the Kiel classification 45% of the tumours were centroblastic multilobated. PLB presented most often in the long bones (48%), with Ann Arbor stage I (46%), II (16%), IV (16%) and unknown (20%). Stage IV disease was exclusively caused by the presence of multiple bone lesions. Notwithstanding the heterogeneous treatment, the 5-year overall survival was 61%; 46% of patients were progression free at 5 years. Patients at presentation older than 60 had a worse overall survival (76% vs 37%, P = 0.0002) and a worse progression-free period (58% vs 28%, P = 0.0073). Patients with the immunoblastic subtype had a worse survival than the centroblastic mono/polymorphic subtype or the centroblastic multilobated subtype (P = 0.015). Primary lymphoma of bone represents an uncommon bone tumour with a relatively homogeneous morphology and clinical behaviour. Compared to other aggressive lymphomas, PLB have a favourable prognosis.

Adolescent↗