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Purpose of Review: As the appropriate management of patients after prostatectomy is still controversial, the two major approaches, adjuvant radiotherapy (ART) vs. prostate-specific antigen-based surveillance and - upon biochemical recurrence - salvage radiotherapy (SRT) are discussed., Recent Findings: Three prospectively randomized clinical trials into ART with 5-12 years median follow-up and overall 1800 patients show a significant gain in freedom from biochemical recurrence after prostatectomy and adjuvant irradiation (hazard ratio ∼0.5). Only one study reported an improved overall survival (hazard ratio 0.72). Patients with pT3 and positive surgical margins are the most likely to profit from ART. Retrospective analyses of adjuvant vs. SRT suggest a similar oncological outcome if SRT is given early after recurrence, that is at a prostate-specific antigen of 0.5 ng/ml or less. Also, toxicity is similar with the two strategies. With positive lymph nodes, hormone therapy and optionally extended field radiotherapy can be recommended., Summary: The alternative ART or surveillance along with SRT after prostatectomy cannot yet be decided on conclusively. Compliance, physical side-effects, psychological aspects and life expectancy should be taken into account when discussing treatment options. Ongoing and planned trials will hopefully identify subgroups that profit most from one or the other strategy.

The choice of treatment options for prostate cancer patients who have undergone radical prostatectomy depends on their risk profile, which is determined by the tumor node metastasis (TNM) status, histopathologic findings, and the pre- and post-radical prostatectomy PSA characteristics. The results of large clinical studies with a 10-year follow-up or more are the backbone of predictive models for risk estimates that incorporate these criteria and also for guideline recommendations. For low-to-intermediate-risk prostate cancer patients and older patients, observation with--in case of biochemical recurrence--early salvage radiotherapy can be advised after R0 resection, thus, avoiding overtreatment. After R1 resection, adjuvant radiotherapy should be considered. Patients with two or more positive lymph nodes and/or with distant metastasis may benefit from adjuvant hormone deprivation therapy. Beyond this rough outline, detailed analysis of subgroups is still required (and ongoing) to enable individually optimized treatment.

Purpose: Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30% of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir., Materials and Methods: Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed., Results: The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8% in 72 patients with persistently detectable PSA after RP and 65.4% in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05)., Conclusion: Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.

Background and Purpose: Today, there is growing concern about radiotherapy induced secondary malignancies. We analysed the incidence and dose dependence of second cancer., Material and Methods: The study includes 12,000 one-year survivors of radiotherapy, treated between 1981 and 2007. For risk estimates a public databank on cancer in Germany served as reference. Contralateral second breast cancer, second oesophageal and colorectal cancer were analysed with retrospective dosimetry. GI-tract data were used for risk modelling., Results: The incidence rate of second cancers (493 cases) was ~1% per year. Contralateral breast cancer was the most frequent entity (relative risk RR=2.8). The scatter-dose gradient (2-3 Gy) across the contralateral breast did not cause a detectable risk gradient. There was an increased risk for second head and neck cancer (RR=5.1) and for male oesophageal cancer (RR=5.8). For both entities, dose response modelling with case-control data predicted maximum curves with peak induction at 1-5 Gy and positive excess absolute risk values at high doses., Conclusions: A survey of second cancer after radiotherapy requires follow-up over decades. Preliminary dose response modelling albeit with low case numbers suggests an increased risk from multiportal techniques. To improve risk assessment, prospective out-of-field dosimetry and long-term multicentre data collection are recommended., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Salvage radiotherapy (SRT) is applied routinely in patients with biochemical relapse after radical prostatectomy (RP). However, only ∼30% of these patients achieve a durable response after 10 years. As a standard, 66 Gy are given, ideally with a PSA below 0.5 ng/ml. We tried to determine more precisely the optimal PSA for starting SRT., Material and Methods: In 301 prostate cancer patients without hormonal treatment, we analysed the impact on the biochemical response (bNED) to SRT of two pre-SRT PSA levels, namely below or above the median of 0.28 ng/ml., Results: The median follow-up time for the entire group was 30 months. In 151 patients, SRT commenced at a PSA ≤ 0.28 ng/ml, in 150 at > 0.28 ng/ml. Eighty-two patients (27%) developed biochemical progression during follow up. The calculated two-year bNED was 74% for the entire group, 78% versus 61% for a PSA ≤ or > 0.28 ng/ml, respectively. In multivariate analysis, pT(3b), resection status, pre-SRT PSA dichotomized at median, PSA post-SRT undetectable, and PSA doubling time were statistically significant independent predictors of progression after SRT., Conclusions: Our findings suggest that a PSA of ≤ 0.28 ng/ml improves bNED compared with a PSA before SRT of > 0.28 ng/ml., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The optimal dose for salvage radiotherapy (SRT) after radical prostatectomy (RP) is still not defined. It should be at least 66 Gy. In the present study, the suitability of PSA regression as a selection criterion for an SRT dose escalation to 70.2 Gy was examined., Patients and Methods: Between 1997 and 2007, 301 prostate cancer patients received SRT after RP at the Charité - University Medicine Berlin, Campus Benjamin Franklin. None of the patients had antihormone therapy prior to SRT. A total of 234 patients received 66.6 Gy. From 2002 on, 67 patients with a PSA decrease during SRT were irradiated with 70.2 Gy. The influence of this selection and dose escalation on freedom from biochemical progression (bNED) was analyzed., Results: The median follow-up of the whole group was 30 months, the median pre-SRT PSA was 0.28 ng/ml. Of the patients, 27% (82/301) developed biochemical progression, 31% from the 66.6 Gy cohort (73/292) and 13% from the 70.2 Gy cohort (9/67) (p = 0.01). The calculated 2-years bNED was 74% for the whole group, 88% vs. 71% after 70.2 Gy and 66.6 Gy, respectively (p = 0.01). In a multivariate analysis, the total dose (p = 0.017), the re-achievement of an undetectable PSA after SRT (p = 0.005), and the infiltration of the seminal vesicles (p = 0.049) were independent parameters of bNED., Conclusion: Our analysis suggests that patient selection during SRT for a dose escalation to 70.2 Gy can improve the freedom from biochemical progression in patients with SRT after RP.

Vinylbenzyl chloride/divinylbenzene gel copolymer beads have been modified using piperidine, hexamethyleneimine, piperazine, 1-(2-aminoethyl)piperazine, and N-cyclohexyl-1,3-propanediamine. These resins were then tested for the sorption of noble metal ions, namely, Re(VII), Pd(II), Pt(IV), and Au(III), from a 0.1 M HCl solution. The effect of these resins on the sorption of other coexisting ions, such as Cu, Ni and Fe, was also studied. Of the resins tested, resin 4 [1-(2-aminoethyl)piperazine groups] showed the highest sorption capacity for Pt(IV) and Re(VII) from single and multicomponent solutions, with the sorption of Pt(IV) from the multicomponent solution (Re, Au, Pd, Pt, Cu, Ni Fe) in 0.1 M HCl reaching 68 mg Pt/g.

Purpose: To characterize second tumors that developed in or near the high-dose areas of a previous radiotherapy, regarding their frequency, entities, latency, and dose dependence., Patients and Methods: 9,995/15,449 tumor patients of the Radiation Oncology Department in Ulm, Germany, treated between 1981 and 2003, survived at least 1 year after radiotherapy. By long-term follow-up and review of treatment documentation, 100 of them were identified who developed an independent second cancer in or near the irradiated first tumor site., Results: Major primary malignancies were breast cancer (27%), lymphoma (24%), and pelvic gynecologic tumors (17%). Main second tumors were carcinomas of the upper (18%) and lower (12%) gastrointestinal tract, head and neck tumors (10%), lymphoma (10%), breast cancer (9%), sarcoma (9%), and lung cancer (8%). Overall median second tumor latency was 7.4 years (1-42 years). For colorectal cancer it was 3.5 and for leukemia 4.3 years, but for sarcoma 11.7 and for breast cancer 17.1 years. The relatively frequent second tumors of the upper gastrointestinal tract were associated with median radiation doses of 24 Gy. By contrast, second colorectal cancer and sarcoma developed after median doses of 50 Gy., Conclusion: The 5- and 15-year probability to develop a histopathologically independent second tumor in or near the irradiated first tumor site, i.e., after intermediate or high radiation doses, was 0.5% and 2.2%, respectively. To identify potentially radiogenic second malignancies, a follow-up far beyond 5 years is mandatory. The incidence and potential dose-response relationship intermediate will be analyzed by a case-case and a case-control study of the Ulm data.

Background and Purpose: Radiation can induce multidrug resistance (MDR) and thus interfere with simultaneous or subsequent chemotherapy. In SW620 colon carcinoma cells, the interrelation of various biological endpoints of MDR was analyzed and the potential of fractionated irradiation and chemoselection to evoke MDR was compared., Material and Methods: To induce/select an MDR phenotype, SW620 were exposed to either 27 Gy in 1.8-Gy daily fractions or to 50% inhibiting concentrations of doxorubicin or cisplatin, given over 6-15 weeks. Expression of genes involved in MDR, including glutathione metabolism, was determined by semiquantitative RT-PCR (reverse transcription-polymerase chain reaction). Efflux was analyzed by flow cytometry after staining with rhodamine-123 or 5-chloromethyl fluorescein diacetate. Apoptosis was monitored after pulse exposure to doxorubicin or cisplatin. Colony-forming assays were performed under continuous drug exposure., Results: A pronounced gene induction was found in MRP2 after cisplatin selection and up to 3 weeks after radiation. LRP was activated only shortly after radiation. Radiation enhanced rhodamine-123 efflux to a similar extent as short-term chemoselection but not as much as long-term drug exposure. Drug-induced apoptosis was slightly delayed in preirradiated cells. Clonogenic growth in the progeny of irradiated cells was less sensitive to cisplatin but not to doxorubicin., Conclusion: Fractionated radiation can induce an MDR phenotype in SW620. However, long-term drug exposure establishes a more efficient selection. Various endpoints are not fully concordant regarding the extent of MDR. Posttranscriptional modifications, pleiotropic regulation, and alternative pathways may cause these discrepancies.

Purpose: To study the radiation response-modifying effect of imatinib (Gleevec) in a squamous cell carcinoma line, PECA., Material and Methods: Cytotoxicity was determined by colony forming and multiplying capacity. Drug stability was shown by HPLC. Multidrug resistance phenotype was studied by rhodamine-123 efflux. Cell-cycle responses were measured by flow cytometry. Homologous recombination repair was determined by Rad51 immunohistochemistry., Results: Inactivating 50% of the PECA cells required approximately 7 microM imatinib. The drug did not decay nor was it degraded during test periods. Drug efflux occurred only to a minor extent. Multiplying capacity but not survival fractions revealed a radioprotective effect of imatinib. There were only minor cell-cycle alterations in the presence of imatinib but the rate of Rad51-positive repair foci was significantly increased., Conclusion: PECA cells apparently lack a highly specific target for imatinib. In cells surviving at high drug concentrations, imatinib may exert a radioprotective effect on multiplying capacity by inducing DNA repair. Under prolonged exposure, drug-resistant cells may show an accelerated recovery from acute or delayed radiation damage.

Purpose: Total body irradiation (TBI) with and without additional radioimmunotherapy (RIT) was examined for renal toxicity after stem cell transplantation., Patients and Methods: Serum creatinine levels of 35 patients (15 female, 20 male, median age 40.5 years, range 17-60 years) after TBI alone and of 23 patients (eight female, 15 male, median age 47, range 16-58 years) after TBI with additional RIT were determined between 10/1997 and 11/1999. TBI was performed by external-beam radiotherapy in six fractions over 3 days with renal doses of 12 Gy in the TBI-alone group and 6 Gy in the group with additional RIT. The mean kidney dose due to the (188)Re-radiolabeled antibody was estimated to be 8.3 Gy (2.3-11.6 Gy)., Results: Within 12 months after treatment, creatinine levels increased from 77 mmol/l (SD +/- 11) to 89 mmol/l (SD +/- 20) for TBI alone and from 78 mmol/l (SD +/- 13) to 144 mmol/l (SD +/- 52) for combined TBI and RIT., Conclusion: Despite a 50% reduction of the external-beam contribution to the kidney dose, the application of approximately 10 GBq (188)Re-labeled anti-CD66 monoclonal antibody with a calculated renal dose of 8.3 Gy (range 2.3-11.5 Gy) led to renal toxicity, as reported previously. In the absence of a positive dose-response relationship for the (188)Re-labeled antibody, the observation may be explained by an underestimation of the biologically effective dose and the inaccuracy of the dose determination at the glomerular level.

Aims: To examine the dose response of DNA damage and its modification by the radiosensitizer, 5-bromo-2'-deoxyuridine (BrdU). The sensitizing mechanism is analyzed with regard to its influence on the induction and repair of DNA double-strand breaks (DSBs)., Material and Methods: Cells from three different human glioblastoma lines, A7, LH and U87MG, were X-irradiated with and without exposure to BrdU. DNA fragments were separated by field-inversion gel electrophoresis (FIGE) and quantified by fluorometry immediately and 24 h after irradiation., Results: In all cell lines, the dose response followed a linear-quadratic rather than a purely linear function. BrdU-treated cells exhibited a significantly higher amount of mobile DNA. In repair experiments with and without BrdU, the amount of mobile DNA fell close to control values within 24 h., Conclusions: The linear-quadratic model appropriately describes the X-ray-induced fragmentation of DNA. BrdU sensitizing acts predominantly by increasing DNA fragility, and not by impairing damage repair. The amount of DSBs persistent after 24 h of repair is minimal, even after highly cytotoxic doses. However, it appears to depend on the extent of initial damage, causing sensitized cells to retain more DSBs than unsensitized cells.

This report summarizes well sampling protocols, data collection procedures, and analytical results for the presence of pesticides in ground water developed by the California Department of Pesticide Regulation (DPR). Specific well sampling protocols were developed to meet regulatory mandates of the Pesticide Contamination Prevention Act (PCPA) of 1986 and to provide further understanding of the agronomic, chemical, and geographic factors that contribute to movement of residues to ground water. The well sampling data have formed the basis for the DPR's regulatory decisions. For example, a sampling protocol, the Four-Section Survey, was developed to determine if reported detections were caused by nonpoint-source agricultural applications, a determination that can initiate formal review and subsequent regulation of a pesticide. Selection of sampling sites, which are primarily rural domestic wells, was initially based on pesticide use and cropping patterns. Recently, soil and depth-to-ground water data have been added to identify areas where a higher frequency of detection is expected. In accordance with the PCPA, the DPR maintains a database for all pesticide well sampling in California with submission required by all state agencies and with invitations for submission extended to all local and federal agencies or other entities. To date, residues for 16 active ingredients and breakdown products have been detected in California ground water as a result of legal agricultural use. Regulations have been adopted for all detected parent active ingredients, and they have been developed regardless of the level of detection.

Background: Our aim was to compare and evaluate apoptosis formation as detected by propidium-iodide (PI)/annexin-V or PI/fluorescein-diacetate (FDA) as dose-response parameters in a human promyelocytic leukemia cell line, HL60., Methods: In exponentially growing HL60 cells, apoptosis was induced by ionizing radiation, hyperthermia, topotecan, and cytosine beta-D-arabinofuranoside. At 4 consecutive days following induction, apoptosis was detected by double-labelling, either with PI/annexin-V or PI/FDA. Forward and side scatter, red (PI), and green (FDA or annexin-V) fluorescence were measured by flow cytometry., Results: While light scatter discriminated between morphologically damaged and undamaged cells, fluorescence differentiated vital, apoptotic, and dead cells. Equal proportions of these three subpopulations were detected by both staining techniques. Occasionally, early and mature apoptoses were identified as distinct clusters. During the 4-day observation period, no pronounced maxima of the apoptotic fractions were obtained with either treatment modality. The gradual increases usually showed a delay of 1-2 days., Conclusions: FDA and annexin-V are equally suitable for detecting apoptosis. Separation improves with time after induction, indicating that, with respect to test specificity, mature apoptoses are superior to early stages. However, the sensitivity towards low rates of apoptosis after weak induction appears limited with both staining procedures., (Copyright 1999 Wiley-Liss, Inc.)

Sequential flow cytometry was performed on 73 metastatic malignant melanomas, derived from 804 primary tumors. Tumor thickness was confirmed an excellent prognostic parameter in primary melanoma, but did not allow reliable predictions in metastatic disease. Also, aneuploidy and genetic heterogeneity, both common in metastatic melanoma, were equally distributed among patients differing in survival time. However, a remarkable acceleration was observed in the generation of abnormal cell lines in patients dying early of metastatic disease.

DNA flow cytometry was carried out on 804 primary melanomas. The data were analyzed with a follow-up of 24-96 months. 57% of the cases were diploid, 32% had one abnormal cell population, and 11% were multiclonal. In 8% of the aneuploid tumors there were cell lines in the hypertetraploid range. A reliable S phase determination was possible in 524 cases. Among these 11% had an S phase exceeding 15%. Using an increased tumor thickness, relapse rate and mortality as criteria of tumor progression, aneuploidy and multiclonality, the occurrence of hypertetraploid cell lines and a high S phase (greater than 15%) proved to be correlated with a poor prognosis.

The authors report a case of twins conjoined at the umbilicus and diagnosed by ultrasound after 19 weeks of amenorrhoea in whom an assessment in utero was carried out using magnetic resonance imaging after the patient had been curarized. A review of the literature on this very difficult problem of conjoined twins has given us the possibility to assess the diagnostic measures as well as the prognosis of this pathology. In particular we point out the results that can be obtained using MRI in utero during the second and third trimesters of the pregnancy.

In this work the way of chemical modification of macroporous polymer sorbents with a styrene-divinyl-benzene++ structure was presented. Their modification with amino acids leads to improvement of hemocompatibility of sorbents and to sorption magnification, particularly of hydrophilic polysorbates. In the work the full physical chemical characteristics of the received products was given and their sorption properties in the relation to urea, vitamin B12 and substances from phosphor-organic pesticides group as well as from barbituric acid derivatives were designated.