Anterior exenteration with subsequent ureteroileal urethrostomy in females. Anatomy, risk of urethral recurrence, surgical technique, and results.
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Biomedical subjects
Publications and source records attributed to G Bartsch.
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Collecting duct carcinoma (CDC) is a rare variant of carcinoma of the kidney with aggressive behaviour. CDC arise from the epithelium of the ducts of Bellini in the distal nephron. A CDC in a 53-year old male patient is characterised both by cytogenetic analysis and comparative genomic hybridisation (CGH). The cytogenetic analysis shows a biclonal karyotype 47,XY,+3[2]/40-44,XY,-12[3], -22[4][cp5]/46,XY[42]. Loss of DNA sequences detected by CGH involves chromosome 1, 2, 9, 11 and 18. Gain of DNA sequences affect chromosome 16 and 20. The characterisation of a CDC in this study represents an additional contribution to the poorly explored CDC.
PURPOSE: We describe postoperative surgical anatomy after orthotopic reconstruction of the lower urinary tract using 3-dimensional (D) computerized tomography (CT) and virtual reality endoscopy. MATERIALS AND METHODS: Electronic beam CT was performed in 39 men and 15 women a mean of 60 years old with an orthotopic ileal neobladder (50) or ureteroileal rectosigmoidostomy (4), followed by 3-D reconstruction of the pelvic anatomical structures using specialized computer hardware and software. The mean interval between surgery and CT was 15 months (range 3 to 110) and the mean interval between 2 subsequent 3-D CT studies in 22 patients was 6 months (range 3 to 9). RESULTS: CT time with the patient on the table was 45 minutes and computerized 3-D reconstruction time with the patient off the table was 4 to 5 hours. The pouch had a smooth ovoid shape in 66 and 82% of the patients on the first and second 3-D CT studies, respectively. Mean length of the antireflux nipple was 4 cm. (range 2.5 to 8) and mean length of the afferent limb was 6 cm. (range 3 to 15). There were no radiologically significant sex specific differences in the shape or dimensions of the urinary reservoirs, except for a tendency toward more acute angles between the pouch and remnant urethra. No pathological findings were visible on 3-D CT that were not also evident on conventional CT. CONCLUSIONS: Three-D CT may be clinically useful for surgical planning of a lower abdominal reoperation or unexplained findings and symptoms in patients with bladder substitutions. Cost and time expenditures for processing preclude its routine use in all cases. Virtual reality endoscopy may be a valuable tool for teaching and scientific purposes.
PURPOSE: In recent years the detection rate for small renal tumors has increased due to the widespread use of advanced diagnostic imaging techniques, which in turn has increased the need for nephron sparing surgery. We investigate whether laparoscopic surgery is a suitable approach to partial resection of small renal tumors. MATERIALS AND METHODS: Between June 1994 and October 1996, 7 patients underwent laparoscopic wedge resection of the kidney for renal tumors up to 2 cm. in diameter. Hemostasis was achieved mainly by bipolar coagulation. In addition, the resection surface was cauterized with an argon beam coagulator and then sealed with fibrin glue. In 1 procedure a novel ultrasonic dissector was tested. RESULTS: All procedures could be completed as planned. The only intraoperative complication was a pneumothorax that resolved spontaneously within 2 days. There were no postoperative complications. Histological examination yielded stage pT1 grade I renal cell carcinoma in 3, stage pT1 grade II in 2 and multilocular cysts in 2 cases. All patients had negative surgical margins. Postoperatively, renal function as assessed by serum creatinine was unchanged. Neither local recurrences nor metastases were observed during a followup of 7 to 35 months. CONCLUSIONS: Our results indicate that laparoscopic partial nephrectomy is feasible for small renal cell carcinoma, and is associated with low morbidity and a low complication rate.
BACKGROUND: Small-cell carcinoma and carcinoid tumors of the prostate display a neuroendocrine phenotype. To some extent, adenocarcinomas of the prostate also express neuroendocrine properties. Prostatic neuroendocrine tumors do not respond to androgen ablation therapy. The regulation of synthesis of chromogranins and their processing into neuropeptides have not yet been studied in neuroendocrine cells of the prostate. We used CRL-5813 cells which were derived from a metastasis from small-cell prostate cancer for studies on steroid receptor expression and chromogranin processing. METHODS: The expression of steroid receptor mRNA in CRL-5813 cells was examined by polymerase chain reaction. The synthesis and secretion of chromogranin- and secretogranin II-derived peptides were investigated by radioimmunoassays and high-performance liquid chromatography in untreated cells and in cells treated with the protein kinase A activator forskolin or basic fibroblast growth factor (bFGF). RESULTS: cDNA fragments for alpha-estrogen receptor and androgen receptor but not for beta-estrogen receptor, progesterone receptor, and glucocorticoid receptor were amplified from CRL-5813 cells. These cells were found to contain typical markers of large dense-core vesicles, i.e., chromogranins A and B and secretogranin II. Forskolin significantly stimulated the synthesis and secretion of the chromogranin B-derived peptide PE-11 and the secretogranin II-derived secretoneurin. bFGF significantly induced PE-11 protein levels in cell extracts. CONCLUSIONS. Our results demonstrate the expression of typical large dense-core vesicle proteins, i.e., chromogranins, in a small-cell prostate cancer cell line and their upregulation by a protein kinase A activator and, in part, by bFGF.
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Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-alpha efficiently silenced mannose receptor-mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-alpha were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.
BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) as the initial test and different diagnostic tests to improve specificity. METHODS: The seven projects studied included 1) a mass screening study using PSA as the initial test in 21,079 volunteers; 2) an investigation of the usefulness of normal and age-referenced PSA cutoffs in 1618 men; 3) a PSA-based screening study of 2272 asymptomatic blood donors; 4) an investigation of the incidence and clinical significance of transitional zone carcinoma in 340 men with negative rectal examination findings and clearly visible prostatic zones on three-dimensional transrectal ultrasound; 5) determination of percent free PSA in one retrospective and two prospective screening studies to define the optimal range of total PSA and determine the appropriate cutpoints for percent free PSA within this range; 6) evaluation of the diagnostic benefit of PSA transitional zone density in 308 screening volunteers; and 7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma diagnosed in 1543 men undergoing transurethal resection of the prostate. RESULTS: 1) Of the 21,078 volunteers, 1618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies (25%) were positive for prostate carcinoma and 135 patients underwent radical prostatectomy. Ninety-five of the 135 pathologically staged lesions (70%) were found to be organ-confined. 2) A PSA cutoff of 2.5 ng/mL in men age 45-49 years and of 3.5 ng/mL in men age 50-59 years with normal digital rectal examination findings resulted in an 8% increase in both the number of biopsies (66 of 778) and the detection rate of organ-confined disease. 3) Of the 2272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined disease in all but eight men. 4) Ninety-eight of 340 men (28.8%) had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transitional zone only. 5) In the retrospective study, receiver operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL were further evaluated and 37 prostate carcinomas were detected. By using a percent free PSA of < or =22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/mL, a percent free PSA of <18%, and normal digital rectal examination findings were further evaluated and 27 (22.5%) were found to have prostate carcinoma. 6) Receiver operating characteristic curve analysis for PSA transitional zone density showed that by using a PSA transitional zone density of >0.22 ng/mL/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing the detection of a single carcinoma. 7) In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a Grade 3 and T1b carcinoma was 2.3%, whereas in the years after the establishment of PSA-based screening the incidence was 4.6% and 1.03%, respectively. CONCLUSIONS: These data suggest that PSA-based screening increases the detection rate of clinically significant and organ-confined tumors. Percent free PSA and PSA transitional zone density provide an additional diagnostic benefit over total PSA.
BACKGROUND: We investigated modulation of androgen receptor (AR) activity in prostatic tumor cells by luteinizing hormone-releasing hormone (LHRH)-induced increase of the intracellular cyclic adenosine monophosphate (cAMP) level. METHODS: AR transactivation activity was assessed in transiently transfected DU-145 and in LNCaP cells. RESULTS: LHRH and cAMP derivative, respectively, induced reporter gene activity to about 15% of the maximal level in DU-145 cells transfected with an AR expression vector and an androgen-inducible reporter gene. LHRH or the cAMP analogue acted synergistically in combination with low concentrations of androgen thus lowering the androgen concentration required for maximal AR activation by a factor of 100. A similar activation of the AR by cAMP analogue was observed in LNCaP cells when enhancement of androgen-induced secretion of prostate-specific antigen was determined. The two nonsteroidal antiandrogens hydroxyflutamide and Casodex(R) inhibited reporter gene activity. CONCLUSIONS: The AR is synergistically activated by low doses of androgen and LHRH or the second messenger cAMP. This may have implications for the treatment of advanced prostate cancer.
BACKGROUND: Both benign and malignant growth of the prostate depend on the induction of a microvasculature. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is thought to play an important role in this process. METHODS: bFGF expression in prostatic carcinoma was assessed by ELISA, reverse transcription polymerase chain reaction, and immunohistochemistry. RESULTS: DU-145 and PC-3 tumor cells produced bFGF. Almost 80-90% of it was localized in the cytoplasm, and 10-20% was associated with extracellular matrix components. Immunohistochemical analysis of prostatic tissue sections showed that cancer cells stained more intensively as compared to putatively healthy epithelium. In prostate cancer patients, mean bFGF serum levels were significantly elevated when compared to a healthy control group (6.64 pg/ml vs. 1.28 pg/ml). Serum bFGF levels did not correlate with any other clinical marker such as PSA, tumor stage, or grade. Four out of five patients who progressed to a more advanced stage showed an increase in serum bFGF levels. CONCLUSIONS: These results suggest that increased bFGF release may be associated with a more aggressive tumor phenotype.
BACKGROUND: In order to assess the value of various new therapeutic modalities in the management of benign prostatic hyperplasia (BPH), we performed a prospective study comparing transurethral resection of the prostate (TURP) to contact Laser, interstitial Laser, and transurethral ultrasound-guided laser-induced prostatectomy (TULIP). METHODS: The following parameters were evaluated preoperatively as well as 3, 6, and 12 months after surgery: prostatic volume, urinary flow rate, postvoid residual volume, and the AUA symptom score. The diagnosis of bladder outlet obstruction was established preoperatively by means of pressure/flow studies which were repeated 1 year after the operation. RESULTS AND CONCLUSIONS: In conclusion, TURP is still the gold standard in the treatment of BPH. The results of TULIP, contact laser, and interstitial laser are about the same. The time intervals within which the patients become free of symptoms, however, vary widely. Contact laser is limited to prostates below 50 cc, while interstitial laser is ideal for patients in poor general health who present with large prostates. Furthermore, our results demonstrate that the only reliable data for determining the degree of posttherapeutic disobstruction can be provided by urodynamic investigations including pressure/flow diagrams.
BACKGROUND: The measurement of prostate specific antigen (PSA) is widely used in screening programs for early detection of prostate cancer. However the specificity for cancer detection is limited because serum PSA is also elevated in patients with benign prostatic-hyperplasia (BPH) and/or prostatitis. It has been shown recently, that the ratio of free/total PSA in serum is lower in malignant prostatic disorders than in non-malignant ones and therefore might be a parameter to improve screening specificity. In a retrospective study, we tested whether free/total PSA helps to distinguish between BPH and prostatic carcinoma in men with elevated serum PSA. METHODS: A total of 266 men have been identified with age-specific elevated serum PSA levels using a conventional PSA determination kit. Subsequently their disease was proven by biopsies. Free and total PSA levels in these serum samples were measured using the DELFIA PSA dual label free/total PSA kit. RESULTS: The mean free/total PSA of 64 patients with prostate cancer was 0.10 and was significantly (P = 0.001) different from the mean free/total PSA of 202 men who were histologically free of cancer, which was 0.17. Receiver-operating-characteristic curve (ROC) analysis showed that using a free/total PSA ratio of 0.18 as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated while still detecting 94% of all carcinomas. CONCLUSIONS: These results show that the ratio of free/total PSA is a useful determination and can improve specificity of prostate cancer screening.
Smooth muscle cells (SMCs) constitute a major cellular component of prostatic stroma. SMC tension plays an important role in urethral obstruction secondary to benign prostatic hyperplasia (BPH). We have developed an in vitro procedure for the propagation of human prostatic SMCs. Tissue specimens from patients undergoing radical prostatectomy or cystectomy were enzymatically disaggregated and cultured in MCDB-131 medium supplemented with horse serum, insulin, conditioned medium from the tumor cell line CRL-5813, and steroid hormones. The medium was assembled on the basis of the effects these supplements have on the growth of SMC cultures and on the expression of the two markers desmin and smooth muscle myosin. Addition of 0.1 microM of estradiol to the growth medium dramatically increased expression of these SMC-specific markers. Dihydrotestosterone (DHT) and hydrocortisone had a similar, albeit less pronounced effect. At three to five passages, about two thirds of the cells were immunohistologically positive for smooth muscle myosin or desmin. Almost all cells were positive for the myofibroblast marker smooth muscle alpha-actin throughout 10 passages and more. In SMC cultures, cells staining for smooth muscle myosin and desmin were found to seek direct contact to myofibroblasts. They grew in aggregates on a layer of myofibroblasts which adhered to the surface of the culture vessel. As revealed by transmission electron microscopy the cultured cells exhibited morphological features of myofibroblasts. Characteristics of smooth muscle cells, such as prominent bundles of microfilaments associated with dense bodies, basal laminae investing the cells, and numerous caveolae at the cell surfaces were regularly observed in cultures of low passages. After several passages, these features were markedly decreased and organelles of the biosynthetic system became more prominent. In summary, we present an in vitro model of prostatic SMCs and demonstrate that steroid hormones have characteristic effects on these cells. SMC cultures are expected to facilitate investigation of the functions and properties of human prostatic SMCs.
Approximately 20% of prostate cancers originate in the transition zone (TZ). Although transrectal ultrasound (TRUS) and systematic biopsies have improved peripheral zone (PZ) cancer diagnosis, additional biopsies directed into the TZ may further improve cancer detection. To evaluate the frequency and clinical significance of TZ cancers, we added two TZ biopsies to the routinely performed sextant biopsies. Three hundred forty patients (aged 45-75) from our prostate-specific antigen (PSA) screening study (21,078 volunteers) with negative rectal examination findings underwent systematic and TZ biopsies with three-dimensional ultrasound equipment. All patients had elevated PSA levels according to age-specific reference ranges. Ninety-eight of 340 men (28.5%) had biopsies positive for cancer. Of these 98 cancers, 28 (28%) originated in the TZ only and 5 (5%) were located in the TZ as well as the PZ. Eight men showed TZ abnormalities on ultrasound images, of whom four had biopsies positive for TZ cancer. The TZ cancers detected were pathologically significant in 96% (27 of 28). Seventy-one percent (20 of 28) of pathologically staged cancers were found to be organ confined and all combined TZ and PZ cancers were advanced tumors. We conclude that TZ biopsies enhance the cancer detection rate in prostate cancer screening and should therefore be added to the routinely done sextant biopsies in men with PSA elevation and normal digital rectal examination findings.
Bacillus Calmette-Guérin (BCG) mycobacteria have been used as adjuvant in the active immunotherapy of various human cancers. In addition, dendritic cells, which are the most potent antigen-presenting cells, have been shown to be capable of initiating anti-tumor immune responses. Here we investigated the effects of BCG on dendritic cells cultured from human blood. Addition of BCG resulted in rapid homotypic adhesion of dendritic cells. Moreover, BCG concentrations ranging from 10(4) to 10(6) bacteria/ml enhanced expression of the dendritic-cell-maturation antigen CD83 and of the T-cell co-stimulator CD86 (B7-2) in a dose-dependent manner. Concomitant with the increase of CD83 and CD86 expression, the cells lost the ability to capture soluble antigens, as determined by the exclusion of fluoresceinated Dextran molecules. Strikingly, the same dosages of BCG-bacteria stimulated TNF-alpha-gene transcription and TNF-alpha-protein release from dendritic cells in a dose-dependent fashion. BCG infection of dendritic cells in the presence of a neutralizing antibody directed against TNF-alpha inhibited CD83 expression by more than 50% indicating that the BCG-induced maturation of dendritic cells was at least partially mediated by dendritic-cell-derived TNF-alpha. The finding that BCG activates the most potent antigen-presenting cells reveals a plausible immunological mechanism of the occasionally observed anti-tumor activity of BCG.
BACKGROUND: The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described. METHODS: In the present study, prostate specific antigen (PSA) samples obtained from 2,272 males (aged 40-65 years) who donated blood at the local Red Cross Blood Bank were evaluated. Two groups of donors were distinguished, which were investigated in different ways. Group 1 comprised individuals aged 40-49 years (n = 568), while group 2 consisted of males aged 50-65 years (n = 1,704). Volunteers in group 2 who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound guided biopsy irrespective of findings on digital rectal examination (DRE). In group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings biopsy specimen was ordered (n = 2). In patients with unremarkable findings on DRE, serum PSA was determined 1 year later and in case of more than 20% increase in the PSA level biopsy was obtained under ultrasound guidance. RESULTS: The biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a screening test, serum PSA determination was superior to digital rectal examination. On digital palpation only 2 presented with abnormal prostates. These 58 patients underwent radical prostatectomy and histological examination revealed organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy specimen yielded prostatic carcinoma. CONCLUSIONS: This study shows that PSA measurement in blood donors is a useful method for recruiting screening volunteers, and therefore represents an additional possibility for early detection of prostate cancer in asymptomatic younger males. Furthermore, it represents an effective tool for following relatively young patients known to have a significant risk of prostate cancer.
Oestrogen receptors (ER) and progesterone receptors (PR) have been reported by several authors in the stromal cells of the human prostate. Controversial results exist on the expression of ER and PR in epithelial cells of the prostate. Some recent publications, in contrast to previous findings, have suggested that these receptors are also present in human prostate cancer cell lines derived from metastatic lesions. The expression of ER and PR in these cell lines has been re-examined to determine their presence in lymph node metastases from patients who did not receive any kind of endocrine therapy and in distant metastases obtained from patients who failed endocrine treatment. ER and PR expression in LNCaP, PC-3, and DU-145 cells was assessed by means of the reverse transcriptase-polymerase chain reaction, ligand binding assays, and immunohistochemistry. With all the techniques applied, the three cell lines were found to be negative for both ER and PR. Immunohistochemical analyses were performed in four lymph node metastases obtained at radical prostatectomy from patients who did not receive endocrine therapy and in 17 distant metastases obtained at palliative surgery from patients who failed endocrine therapy. All 21 metastases were negative for ER and PR on immunohistochemistry. These results do not support the recently developed concept that receptors for oestrogenic and progestagenic steroids are present in metastases from human prostate cancer.
The emerging experience in urethra-sparing cystectomy in women undergoing subsequent orthotopic lower-urinary-tract reconstruction with regard to the anatomy of the remnant urethra, patient selection, refinements of the surgical technique, the patients' outcome with respect to the underlying disease, the risk for tumor recurrence, and postoperative urodynamics are the main focus of this report. In the present study, 30 carefully selected female patients underwent orthotopic reconstruction of the lower urinary tract. Surgical variations emerging from the first learning curve, including nerve-sparing anterior exenteration, vaginal reconstruction, omental support of the neobladder floor, and ureterointestinal anastomosis, were applied in 21 patients with lower-urinary-tract reconstruction. Of 24 patients followed for more than 6 months, 21 (87.5%) are continent at daytime, 19 (79%) have nocturnal continence, and only 1 (4%) requires self-catheterization; 3 patients with urinary retention were successfully treated for obstructed ileal valves. After a follow-up period of 2-41 (mean 15.4) months one patient each developed local recurrence (uterine adenosarcoma) after 13 months and distant metastasis transitional-cell cancer of the bladder after 3 months; all other patients are currently free of disease. Urethra-sparing surgery has established itself in selected women with bladder cancer. Refinements in the technique of radical cystectomy and orthotopic creation of a neobladder to the urethra may improve the continence, spontaneous micturition, and surgical oncological outcome of these patients.