Elephantiasis of the legs with lichen sclerosus et atrophicus of the penis and scrotum.
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Aged↗
Biomedical subjects
J Breul
Publications and source records attributed to J Breul.
5-Fluorouracil versus folinic acid and 5-fluorouracil in advanced, hormone-resistant prostate cancer: a prospective randomized pilot trial.
OBJECTIVES: Results of cytotoxic chemotherapy for hormone-resistant prostate cancer are not impressive. One of the substances which seems to have a therapeutic benefit is 5-fluorouracil (5-FU). The effect of 5-FU can be modulated by addition of folinic acid (FA). We tested in a prospective, randomized phase II trial monotherapy with 5-FU versus the combination of 5-FU and high-dose FA. METHODS: 25 patients received 600 mg/m2 5-FU, and 24 patients 400 mg/m2 FA plus 600 or 400 mg/m2 5-FU. They were treated for two cycles for 5 days in a 21-day interval followed by a weekly single-day application until progression occurred. Pain remission, toxicity, time to progression and survival were evaluated. RESULTS: Both regimens led to a pain remission in nearly 70% of the patients. Mucosal side effects like diarrhea and stomatitis occurred more often in the combination arm, whereas leukopenias were more frequent in the monotherapy are. We observed no statistically significant difference between the two treatment arms regarding time to progression and survival. CONCLUSIONS: Although both regimens led to a pain remission, side effects are too severe to recommend these protocols for standard treatment of hormone-resistant prostate cancer.
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Enhancement of 5-fluorouracil cytotoxicity by folinic acid in different cell-lines of human renal cell carcinoma.
Results of cytotoxic chemotherapy in metastatic renal cell carcinoma are not impressive. Remission rates range between 0 and 20%. One of the substances which show a marginal effect is 5-fluorouracil (5-FU). The cytotoxicity of 5-FU can be modulated by combination with folinic acid as shown in various cell lines and clinical trials. We were interested to see whether such a biomodulation also occurs in renal cell cancer. The antiproliferative effect of 5-fluorouracil on two human cell lines of RCC and its potentiation by folinic acid was investigated in a monolayer proliferation assay. It could be shown that folinic acid enhanced the cytotoxic potential of 5-FU 6-8-fold. Our results indicate that the combination of these two drugs in the treatment of metastatic renal cell cancer might lead to better response rates.
Carcinoma, Renal Cell↗
Rare metastases of signet ring cell carcinomas to the scrotum: report of two cases.
Metastases of signet ring cell carcinomas to the scrotum are rare. We present 2 patients with this kind of tumor. In 1 patient, the scrotal pathologic examination helped to detect an adenocarcinoma of the appendix with a signet ring cell component, with an extent that had not been apparent clinically. The other patient was seen at an advanced stage of signet ring cell carcinoma of the sigmoid colon following surgical therapy and palliative chemotherapy. The route of metastases seems to be via seeding along the testicular cord and via lymphatic dissemination.
Appendiceal Neoplasms↗
Biomodulation of 5-Fu cytotoxicity by folinic acid and its stereoisomers: in vitro experiments with different cell lines of prostatic cancer.
The results of cytotoxic chemotherapy for advanced, hormone-escaped prostate cancer have been disappointing. Evaluation of the effect of new drugs or new combinations with already known ones is required. The antimetabolite 5-fluorouracil (5-FU) has been shown to be active in prostate cancer, acting via inhibition of thymidylate synthase, an essential enzyme in DNA de novo synthesis. Experiments with cell lines of different tumors have shown that 5-FU activity can be modulated by addition of the coenzyme tetrahydrofolic acid (folinic acid). We investigated the effect of folinic acid and its stereoisomers on 5-FU action in different cell lines of prostate cancer. It was found that addition of non-toxic folinic acid led to a two- to fourfold better antiproliferative effect of 5-FU. The unnatural 6R isomer, which is a compound of chemically synthesized folinic acid, inhibited the modulatory effect of the natural 6S isomer. Our results indicated that a combination of folinic acid and 5-FU may result in a better response of patients with hormone-resistant prostate cancer than of patients treated with 5-FU alone.
Antineoplastic Agents↗
Prostate-specific antigen density and age-specific prostate-specific antigen values: the solution of prostate cancer screening?
The results of 225 systematic prostate biopsies from 1992 to 1993 were evaluated retrospectively. The parameters prostate-specific antigen (PSA) density and age-specific PSA values were compared with digital rectal examination, transrectal ultrasound, and PSA as single parameters and possible combinations. The PSA density proved to have the highest specificity of all single parameters, but the sensitivity was low. Age-specific PSA values are offering a good compromise of sensitivity and specificity as compared with fixed cutoff levels. Since there is no sufficient screening parameter up to now, a combination of all parameters is recommended for screening of early prostate cancer.
Aged↗
Numerical abnormalities of chromosome 7 in human prostate cancer detected by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections with centromere-specific DNA probes.
Fluorescence in situ hybridization (FISH) using chromosome-specific alpha-satellite DNA probes for chromosomes 7, 8, and 12 was performed on paraffin-embedded tissue sections and touch imprint preparations of 53 cases of human prostate cancer. Subsequent haematoxylin and eosin (H & E) staining of the hybridized tissue sections allowed unambiguous assignment of hybridization signals either to tumour or to non-tumorous parenchyma. Fifty-three cases of human prostate cancer were evaluated for numerical aberrations of chromosome 7. Scoring 200 cells of tumour and non-tumorous parenchyma in each case revealed abnormalities exclusively in tumour parenchyma in 41 cases (77 per cent). Ten of 41 cases (24 per cent) showed trisomy 7, and 15 cases (37 per cent) monosomy 7 or trisomy 7 in combination with monosomy 7, respectively. Sixteen cases (39 per cent) exhibited polysomy 7 in cells of the tumour parenchyma. In the tumour tissue in one case, different polyploid clones (triploid, tetraploid) and polysomy 7 could be identified by double hybridization with chromosome-specific DNA probes for chromosome 7, plus 8 or 12. The indicated numerical aberrations of chromosome 7 were correlated with 78 per cent of advanced pathological stages or poorly differentiated tumours (pT3/4 or G3) of prostate carcinomas. A statistical analysis of the data revealed significant relationships of particular numerical abnormalities of chromosome 7 to different pathological categories (pT, G, pN) of tumour classification. For the T-classification, the frequency of cells carrying polysomy 7 and polysomy 7/+7 increases significantly from pT1 to pT3/4 (P = 0.022).(ABSTRACT TRUNCATED AT 250 WORDS)
Centromere↗
Two-phase short-term culture method for cytogenetic investigations from human prostate carcinoma.
An improved technique for primary short-term culture of prostate carcinoma cells in two phases, with and without serum, for subsequent cytogenetic analysis is reported and compared with four other methods. After mechanical disaggregation and a brief collagenase treatment of tumor specimens, cell clusters were seeded in RPMI 1640 and 15% fetal calf serum (FCS) without any other supplement in the first phase. The culture medium was changed to a serum-free medium supplemented with bovine pituitary extract (BPE) and epidermal growth factor (EGF) when the first outgrowth became apparent. During this second phase, fibroblast growth could be virtually abolished within 48 hr. The epithelial and prostatic origin of the cultured cells was confirmed by immunocytochemical methods in each culture. Metaphase analysis revealed chromosome aberrations in over 80% of cases (both clonal and nonclonal alterations) indicating the presence of neoplastic cells. Clonal numerical chromosome aberrations, found by conventional cytogenetic analysis, were used to provide the reliability of the culture system in interphase nuclei of corresponding uncultured tumor tissue by fluorescence in situ hybridization (FISH). The main points of the described method are: 1) combined mechanical/enzymatic disaggregation, 2) seeding of the disaggregated cell clumps rather than of single cells, 3) initialization of the cultures in RPMI 1640 medium with 18% FCS without any other supplements, and (4) stimulating of selective epithelial proliferation by changing the culture conditions through serum-free medium.
Antigens, Neoplasm↗
Prostate-specific antigen in urine.
We investigated concentrations of prostate-specific antigen (PSA) in mid-stream urine of 213 patients. Among them were 34 females. Diagnoses of the male patients were 42 benign prostatic hypertrophy (BPH), 21 localized prostate cancer prior to radical prostatectomy (RP), 15 post-RP without distant or local recurrence, 5 post-RP with local recurrence and 82 with other urological diseases. PSA levels were determined by the Hybritech Tandem E method. Female urine samples were positive in 38% of the cases. This and the finding of PSA in urine of men after RP is most likely due to extraprostatic production by periurethral glands. Urinary PSA levels do not differ between patients with BPH, organ-confined prostate cancer and other diagnoses. In some cases, however, urine PSA levels can be elevated in men with local tumor recurrence after RP when serum levels are still undetectably low. This indicates that the determination of urinary PSA concentration might be useful in the follow-up of patients after RP.
Biomarkers, Tumor↗
High resolution image-cytometric differentiation of hormone sensitive and hormone insensitive prostatic carcinomas.
Until the present it was not possible to predict hormone sensitivity of prostatic carcinoma. Based on studies correlating image cytometric results of hormone receptor negative and hormone receptor positive breast carcinomas, the present study aims at separating responders and non-responders to hormone therapy in metastatic prostatic carcinoma. From May-Grünwald-Giemsa stained slides of fine needle aspirates of 23 patients with metastasizing prostatic carcinoma about 100 nuclei per slide were taken by TV camera for image-cytometric processing. One thousand and twenty-two nuclei came from 10 patients who showed tumour regression for at least 36 months and who all survived for more than 5 years. One thousand three hundred and thirty-two nuclei were from prostatic aspirates of patients who showed a continuous tumour progression despite receiving hormone therapy. All patients of the latter group died within 5 years. A correct classification of the patient groups of responders and non-responders was possible in 19-21 of 23 cases by means of high resolution image analysis including nuclear structural features. It was found that even simple planimetric features, like the nuclear perimeter, or densitometric features, such as the total nuclear extinction, differed markedly between the two groups. The data show that nuclei from hormone sensitive prostatic carcinoma are distinct from those of non-sensitive ones in the present series. The interpretation of results must take into account that the very strict criteria for hormone sensitivity leads to a highly selected patient group. The application of the method to an unselected patient group can be presumed to yield a higher rate of false classifications.
Azure Stains↗
[Reconstruction of the bladder neck after radical retropubic prostatectomy using a tubular bladder flap].
To improve urinary continence after retropubic prostatectomy, especially in the early postoperative phase, we used a 1.5 cm tubularized anterior bladder flap for bladder neck reconstruction in 30 patients. We compared the continence rates of these patients with 30 patients with standard bladder neck closure operated on in the same period of time. Continence rates were assessed by a personal interview 1 day after catheter removal (postoperative day 22) and 3 months postoperatively by a questionnaire. While only 2/30 (6.6%) of the patients with standard bladder neck closure were completely continent 1 day after catheter removal, 9/30 (30%) of the patients with the tubularized neourethra were completely dry. After 3 months the standard procedure led to a 58% rate of complete continence. This was achieved in 75% of patients with the tubularized flap. Ten percent of the patients with conventional operations developed a bladder neck contracture. This complication occurred in 20% of the patients with the new method. Analyzing subgroups, we found that patients with a tubularized neourethra who received adjuvant irradiation of the prostatic bed because of positive surgical margins developed a bladder neck stenosis in 40% of the cases due to shrinking of the flap.
Adult↗
Implantation metastasis after a suprapubic catheter in a case of bladder cancer.
We report about a patient who was treated with a percutaneous suprapubic cystostomy in order to relieve repeated urinary retention. Two hours later a bladder tumor was found and the suprapubic catheter was removed. After transurethral resection of the bladder tumor the histological specimen showed a pT3 G3 squamous cell carcinoma. Because of the age and reduced performance status of the patient a radical cystectomy was contraindicated. In a second approach we performed again a transurethral resection of the bladder tumor simultaneously with a resection of the prostate. Eight weeks later the patient was admitted to our hospital because of reduced performance status and gross haematuria. We found a widespread bladder tumor with an implantation metastasis in the abdominal wall at the site where the suprapubic catheter was placed and multiple lung metastases. The patient died within one week after admission. The literature is reviewed and therapeutic strategies are discussed.
Aged↗
Effect of digital rectal examination on serum concentration of prostate-specific antigen.
Prostate-specific antigen (PSA) is used for screening and follow-up of patients with prostate cancer. The effect of certain diagnostic procedures on PSA serum levels is not well defined. Therefore, the effect of digital rectal examination (DRE) on PSA serum levels was investigated. No significant difference was observed in PSA values before and after DRE when blood samples were taken 1-3 min after palpation of the prostate. Kinetic studies demonstrated a significant increase in PSA values up to the factor 3.2 in 14 of 19 patients 2-6 h after DRE. In 9 of 14 cases, PSA was within the initial range 24 h after DRE. That means that a urologist is allowed to take blood samples for the determination of PSA at least within 3 min after palpating a suspicious prostate without getting false-positive results.
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[Pedicled penis skin flap for unilateral correction of extensive urethral strictures including meatus reconstruction].
Many techniques have been described for the repair of recurrent urethral strictures. We report our experience with the use of vascularized island skin flap repairs of urethral strictures as a one-stage procedure in 24 patients and describe the rationale for selection of the procedure, surgical technique used, results and complications. Using the pedicled penile island flap and the inner preputial skin one-stage correction is possible in urethral strictures up to the tip of the penis. The combined use of scrotal skin increases the risk of complications and thus should be avoided. Meatal reconstruction as described by De Sy gives excellent functional and cosmetic results.
Adolescent↗
Formulation of interleukin-2 and interferon-alpha containing ultradeformable carriers for potential transdermal application.
INTRODUCTION: Transfersomes (TF) are new highly deformable hydrophilic lipid vesicles, which are able to spontaneously penetrate the skin barrier because of their characteristics. Transfersomes are able to transport non-invasively low as well as high molecular weight molecules into the body. We describe the formulation and several biological characteristics of Interleukin-2 and Interferon-a containing TF. MATERIAL AND METHODS: TF contain natural phosphatidylcholine and sodium cholate. Recombinant human IL-2 and human hybrid interferon-alpha A/D were added to TF and incubated for 24 hours at 4 degrees C. Immunotransfersomes were isolated from free IL-2 and IFN by filtration (Centrisart, Sartorius). Biological activity of immunotransfersomes was measured by CTLL-cell-assay for IL-2 and by A549--EMCV-assay for IFN, concentrations of proteins by ELISA. RESULTS: It has been possible to incorporate a high amount of IL-2 and IFN in TF (75-80%). Incorporated IL-2 and IFN were biological active. The increase of the proportion of lipid to protein to 90.9/1 led to growing probability of association. CONCLUSION: We were able to show, that IL-2 as well as IFN is trapped by transfersomes in biological active form and in sufficient concentrations for immunotherapy. In upcoming experiments these IL-2 and IFN-containing TF are used for a transdermal approach in the murine RENCA cell line model.
Administration, Cutaneous↗