[Rational follow-up of non-muscle invasive bladder cancer]. / Rationale Nachsorge des nicht-muskelinvasiven Harnblasenkarzinoms.

BACKGROUND: Follow-up for non-muscle invasive bladder cancer (NMIBC) is a challenge for urologists that has not been finally resolved. The intensity of follow-up is based on the recurrence and progression behavior of the tumor as well as the patient's individual situation. MATERIALS AND METHODS: The following article focuses on the current data situation, the valid German S3 guideline and the available instruments for the detection of relapses and progression, taking into account tumor stages and degree of malignancy. RESULTS: Urethrocystoscopy, imaging and urine cytology are generally recommended, but the recommendations appear to be too extensive in the case of so-called intermediate risk profiles. Depending on the situation, urine markers could optimize follow-up, although results from prospective randomized studies are still pending. CONCLUSIONS: The current follow-up of NMIBC is invasive, carries the risk of side effects and increases costs. In the absence of scientific evidence, recommendations for follow-up for NMIBC are naturally based on expert opinion. In the opinion of the authors, overdiagnosis is currently taking place particularly in patients with an intermediate risk profile. The first prospective, marker-based studies are ongoing and will be helpful in the near future to improve the data situation relevant to urological practice.

[Active surveillance in prostate cancer]. / Active Surveillance beim Prostatakarzinom.

Prostate cancer remains among the most commonly diagnosed malignancies worldwide in men. In patients with low-risk prostate cancer, the risk of metastasis and mortality is very low; therefore, a tumor surveillance strategy can be used. In patients undergoing active surveillance, curative active therapy is postponed without compromising opportunities for cure until there is evidence of progression or the patient desires active therapy. The aim of active surveillance in prostate cancer patients is to minimize treatment-related toxicity without impairing patient survival. To maintain patients under active surveillance, the following criteria should be met: prostate-specific antigen (PSA) ≤10 ng/ml, Gleason score ≤6, cT1 or cT2a, ≤2 biopsy cores with <50% cancer involvement of every positive core. Follow-up in active surveillance patients is based on repeat biopsy, serial PSA measurements, and digital rectal examination.

Comparison of T-cell-depleted BMT and PBPCT with respect to chimerism, graft rejection, and leukemic relapse.

Chimerism analysis by DNA-based methods is a valuable diagnostic tool for monitoring engraftment and leukemic relapse after allogeneic BMT or PBPC transplantation (PBPCT). We investigated the chimerism after T-cell-depleted BMT (n = 32) in comparison with T-cell-depleted PBPCT (n = 39). BM grafts were T-cell depleted using the Campath-IgM antibody plus complement. For T-cell depletion of the PBPC grafts, a selection of CD34+ cells with or without a subsequent CD2/3 depletion was performed. In all patients, the T-cell dose of the transplant was < 10(6)/kg body weight. Between day 13 and day 120 after transplantation, chimerism analysis was done by RFLP or amplified fragment length polymorphism (PCR-AFLP), with a detection limit of 1%-5% recipient cells. In the BMT group, 8 of 32 (25%) patients showed a mixed chimerism, but only one graft rejection and no leukemic relapse occurred after a median follow-up of 41 (3-84) months. All patients with PBPCT revealed a complete chimerism of their granulocytes, and 38 of 39 patients showed complete chimerism of their lymphocytes. Follow-up time in these patients is 7 (2-21) months, with no graft rejection and two leukemic relapses. G-CSF-mobilized PBPC are superior to BM cells for full engraftment even after T-cell-depleted transplantation. The more relevant factor for developing complete chimerism seems to be the quantity and possibly the quality of the stem cells rather than the residual T-cell load of the graft. However, a mixed chimerism of the lymphocytes early after transplantation does not predict a higher rate of graft rejection or leukemic relapse.

Collection of allogeneic peripheral blood progenitor cells by two protocols on an apheresis system.

BACKGROUND: Granulocyte-colony stimulating factor-mobilized allogeneic peripheral blood progenitor cells (PBPCs) are replacing bone marrow in transplantation for the treatment of several hematologic malignancies. The advantages of PBPCs are offset by the donor-associated disadvantages of granulocyte-colony stimulating factor side effects and the risk of apheresis-like platelet loss. STUDY DESIGN AND METHODS: For each individual, the first donation of allogeneic PBPCs by apheresis on the Spectra, using either the standard protocol Version 4.7 (45 donors, [Version 4.7]) or the AutoPBSC (60 donors, [AutoPBSC]) was compared. Between July 1995 and May 1996, all donors enrolled underwent Version 4.7 apheresis. Since May 1996, the majority of donors underwent AutoPBSC apheresis. For statistical analysis, only data from the first apheresis for each individual donor was considered for independent values. RESULTS: These results indicate a similar collection efficiency for CD34+ cells in the first apheresis of each donor (54% Version 4.7 vs. 53% AutoPBSC, p = 0.8). The apheresis time was longer with the AutoPBSC (233 min vs. 251 min, p = 0.005), whereas the loss of platelets was significantly lower (p < 0.001) with the AutoPBSC (28% vs. 19%). The mean number of CD34+ cells collected in the first apheresis component was 4.0 x 10(8) (Version 4.7) versus 3.8 x 10(8) (AutoPBSC). CONCLUSION: Both apheresis protocols collect sufficient numbers of PBSCs for allogeneic transplantation. The AutoPBSC operates in a fully automatic fashion, avoiding manual adjustment and interindividual variations. The loss of platelets is lower with AutoPBSC than with Version 4.7, but the apheresis time is slightly longer.

Haematopoietic reconstitution after autologous transplantation of CD34(+)-selected versus non-selected peripheral blood progenitor cells.

Selection of CD34+ cells for autologous transplantation is increasingly being used to reduce potential tumor cell contamination of the autograft. Haematopoietic reconstitution in 40 patients after transplantation of CD34(+)-selected versus non-selected G-CSF-mobilized PBPC was compared and was almost identical in the two groups of patients. Delayed platelet engraftment was only observed in patients transplanted with a CD34+ cell dose of < 2.5 x 10(6)/kg body weight. It has to be shown whether the positive selection of CD34+ cells will improve the disease free survival after autologous PBPC transplantation.

Combined CD34 positive plus CD2 negative selection for effective T-cell depletion as GvHD-prophylaxis in HLA-nonidentical blood progenitor cell transplantation.

G-CSF mobilized, T-cell-depleted peripheral blood progenitor cells (PBPC) and T-cell-depleted bone marrow (BM) were given to seven children (6 AL, 1 SCID) to prevent severe graft-versus-host-disease (GvHD) as well as graft rejection after transplantation from HLA-nonidentical parental donors. BM was T-cell-depleted by lectin agglutination and E-rosetting. For T-cell-depletion of the PBPC grafts a combination of CD34+ selection with the Ceprate SC immunoadsorption system and a subsequent depletion of CD2+ cells with immunomagnetic Dynabeads was used. The overall recovery was 0.3 (0.1-1.2)% for nucleated cells, 29 (18-45)% for CD3+ cells, respectively. The purity of CD34+ cells was 87 (68-97)% with a 0.3(0.05-0.7)% residual CD3+ T-cell contamination. In spite of the large T-cell number in the PBPC grafts the combination of CD34 positive and subsequent CD2 negative selection achieved a more than 4 log T-cell depletion and prevents severe GvHD even in HLA-nonidentical transplantation. In addition, if a high dose of progenitor cells ensures stable engraftment, this new approach could increase the possibility of wider use of HLA-mismatched family donors for transplantation.

Improved lectin agglutination method for T-cell depletion of HLA-mismatched bone marrow grafts in children.

For T-cell depletion in HLA-nonidentical bone marrow transplantation of children with malignant diseases, we improved the original lectin/rosetting method described in 1981 by adding anti-CD2/3 coated donor red blood cells to the combination to achieve lectin agglutination in one step. Further improvements in handling led to a shortened and simplified method and better quality of the graft. Five bone marrow grafts prepared with this modified protocol contained a median number of 6 (0-28) x 10(4) T-cells per kg, corresponding to 0.02 (0-0.08)% CD3+ cells and 6 (3.7-10.5) x 10(6) CD34+ cells per kg at a median body-weight of 7 (5-38)kg. The overall recoveries after T-cell depletion were: NC 17 (10-44)%, CD34+ cells 61 (22-100)%, and CFU-GM 55 (29-212)%.

Chimerism analysis after allogeneic bone marrow transplantation with nonradioactive RFLP and PCR-AFLP using the same DNA.

We describe a method combining RFLP and PCR-AFLP analyses for studying chimerism after allogeneic bone marrow transplantation. Using RFLP analysis alone with DNA probe hMFl 87% of 244 donor/recipient pairs revealed different specific bands. By examination of the identical DNA probes using PCR-AFLP, an additional 52% of the residual donor/recipient pairs could be identified. Thus, 94% of allogeneic transplantations can be monitored using a combination of RFLP and PCR-AFLP analyses at one locus.

Proficiency testing of water microbiology laboratories in The Netherlands.

In a 3-year period, four series of simulated water samples containing selected test strains were distributed to more than 50 laboratories in The Netherlands for bacteriological testing. Participating laboratories examined the samples by enrichment or membrane filtration methods, or both, for total coliform organisms, thermotolerant coliform organisms, faecal streptococci and standard plate counts (37 degrees and 22 degrees C) according to Dutch standard methods. The results were quantitatively satisfactory: the distribution of positive and negative results with subsamples conformed to stochastic variation; the standard deviation of membrane or plate counts was usually in the range which may be expected from a Poisson distribution, and there was good correspondence between average counts in participating laboratories and those expected from controls in the organizing laboratory. Problems of a qualitative nature were frequently encountered, however. Among them were a false positive response with a strain of Enterobacter cloacae in the thermotolerant coliform test; a false positive result with Clostridium perfringens in enrichment tests for total or thermotolerant coliform organisms and false positive results with Micrococcus varians in the faecal streptococcus test by membrane filtration. It is concluded that quality assessment should be a consistent activity in water microbiology laboratories. For this purpose, stable and well characterized reference materials are needed.

Survival of Salmonella spp., Staphylococcus aureus and Bacillus cereus in "Advocaat".

Egg yolk and advocaat (a liquor consisting of egg yolk, saccharose and spirit; final ethanol concentration 17.2 vol%) were artificially contaminated with Salmonella (5 serotypes), Staphylococcus aureus (3 phage types) and Bacillus cereus (1 strain), Inoculated egg yolk was used to produce advocaat, Within 24 h after inoculation, the number of Salmonella and S. aureus in the laboratory-prepared advocaat and in the commercially-made advocaat decreased 5 log units or more, It was concluded that the killing effect of ethanol on Salmonella and S. aureus in advocaat was equal to pasteurization, Results also suggest that recontamination of advocaat with Salmonella or S. aureus would cause no public health risk. Spores of B. cereus survived in the product for up to 6 months. B. cereus could be isolated from all 20 samples of advocaat of 6 different manufacturers, Serotyping suggested factory-related B. cereus strains.

Epidemiological studies on Salmonella in a certain area ("Walcheren Project") V. Studies into the possibility of fattening pigs free from Salmonella.

Studies performed some years ago showed that Salmonella-free pigs for slaughter could be produced under experimental conditions if a number of hygienic measures were taken, such as the purchase of Salmonella-free piglets, the use of properly pelletized feed, thorough cleaning and disinfecting of the pigsty and the prevention of all contamination from the surroundings. In this paper four trials are described which examined whether pigs could also be fattened free from Salmonella under practical conditions on the farm. For this purpose one pigsty on a Salmonella-contaminated farm was used, in which the aforementioned hygienic measures were taken. Despite all these precautions it proved impossible to obtain Salmonella-free pigs. In fact, in three of the four experiments a massive Salmonella infection became manifest among the pigs. The experiments revealed a number of ways in which contamination might have occurred. The existence of these routes of infection was caused by the fact that the measures described above were not carried out accurately, an indication that it will be very difficult to meet the hygiene requirements under farming conditions. Further experiments will have to ascertain whether this is generally the case. In the third and fourth trials, the investigations were not confined to the farm, but were also extended to the period of slaughtering. These made it clear that transportation as well as the waiting time in the slaughterhouse also provided many opportunities for contamination of the pigs, in spite of extensive cleaning and disinfecting of both the cattle-truck and the lairages.

[Epidemiological studies on Salmonella in a particular area ('Walcheren Project'). V. Studies on the possibility of fattening pigs free from Salmonella (author's transl)]. / Epidemiologisch Salmonella-onderzoek in een bepaald gebied ('Project Walcheren'). V. Onderzoek naar de mogelijkheid varkens onder praktijkomstandigheden Salmonella-vrij te mesten.

Four trials were made to study the possibility of fattening pigs free from Salmonella under field conditions. One pig-sty on a Salmonella-contaminated farm was used in these studies. Previous studies had shown that Salmonella-free fattening pigs could be produced under experimental conditions. A number of hygienic measures were adopted on the farm, such as the purchase of Salmonella-free piglets, the use of correctly pelleted feed, thorough cleaning and disinfecting of the pig-sty, and the prevention of all infections originating from the environment. Notwithstanding all these measures, completely Salmonella-free pigs could not be obtained. In three out of four experiments, even a mass infection with Salmonella even became apparent among the pigs. During the experiments a number of possible routes of infection were detected. The presence of these possible routes of infection was due to the fact that the measures referred to were not carried out accurately. This suggests that it will be very difficult to satisfy the requirements of strict hygiene under field conditions. Further experimental studies will have to show whether this is usually the case. During the third and fourth trial, studies were not confined to the farm, but also extended to the period of slaughter. From these investigations it became apparent that transport to as well as the period of waiting in the slaughter-house also provide several opportunities for contamination of the pigs, in spite of extensive cleaning and disinfection of both cattle-truck and lairages.