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Biomedical subjects

Rainer Hofmann

Publications and source records attributed to Rainer Hofmann.

31 records · Page 2Linked to original sources

Magnetic resonance urography in pediatric urology.

OBJECTIVE: To evaluate the efficiency of magnetic resonance urography (MRU) in pediatric urology. MATERIAL AND METHODS: We report retrospectively on 12 children who underwent MRU between January 1999 and November 2001. MRU was performed to accurately evaluate the entire urinary tract because of megaureter, ectopic ureter, vesicoureteral reflux, Y-inverted duplication and hydronephrosis because of pyeloureteral stenosis. T1- and T2-weighted images were obtained in the coronal, sagittal and axial planes. The mean age of the children (8 females, 4 males) investigated was 36 months (range 2-140 months). RESULTS: An accurate anatomical picture of the entire urinary tract could be obtained in all children. The obstructive nature of megaureter could be differentiated. The distal orifice of ectopic ureter could be identified in the vagina. Vesicoureteral reflux into the blind-ending ureteral bud of a duplicated system was accurately identified. Hydronephrosis was demonstrated to be the result of pyeloureteral stenosis. The location of stenoses was easily identified in the sagittal and coronal planes. CONCLUSIONS: MRU is an excellent imaging modality for accurately depicting the urinary tract. MRU is superior to conventional intravenous urography because it does not use ionizing radiation, the gadolinium contrast medium used is not nephrotoxic and the imaging quality is excellent, reproducible and not interfered with by gas superposition. Considering the high costs and diagnostic benefit of MRU compared to intravenous urography, MRU should be performed in patients with impaired renal function, in those with an allergy to contrast medium and if anatomic relationships are not clear prior to reconstructive surgery.

Age Factors↗

Application of real-time reverse transcriptase-polymerase chain reaction in urological oncology.

PURPOSE: During the last decade numerous different reverse transcriptase-polymerase chain reaction (RT-PCR) techniques have been described. However, the lack of highly sensitive, quantitative and reliable methodology has been responsible for its limited use in modern urology. Early semiquantitative RT-PCR techniques often proved not to produce consistent results and have a high failure rate due to complicated working models. In this article we provide a comprehensive and intelligible description of real-time PCR technology, which is a novel quantitative methodology to analyze gene expression. In addition, we report the first preclinical and clinical applications in molecular urology. MATERIALS AND METHODS: The current literature was reviewed in regard to different current real-time RT-PCR protocols and their use in modern urological oncology. RESULTS: Real-time RT-PCR is a reliable, rapid and relatively inexpensive technique that can be easily adapted for standardized preclinical and clinical applications at different centers. Its sensitivity equals at least that of conventional RT-PCR and the option of exact quantification of gene expressions allows proper differentiation among high, low and illegitimate RNA transcription. It eliminates post-PCR processing of PCR products, thereby, increasing throughput and decreasing the chance of carryover contamination. CONCLUSIONS: Although the application of real-time RT-PCR has gained wide acceptance in urological research, its routine clinical use is still in its infancy. However, due to its high sensitivity and exact quantitation real-time RT-PCR may be the method of choice for modern preclinical and clinical studies in the future.

Humans↗

Operative fetoscopical management of intrauterine obstructive uropathia by urethral stent.

We report on an innovative therapeutic attempt in a case with obstructive uropathia in a fetus. Placement of an anterograd urethral stent was performed in the 26th gestational week. Transurethral catheterization via the fetal megacystis, the urethra and the orificium externum of the penis was feasible during fetal endoscopy (Fetendo). During serial ultrasound scans from the 27th to the 36th gestational week a normalization of the amniotic fluid volume was observed. The postpartal evaluation demonstrated that the kidney structure, values of kreatinin serum levels and renal clearance were in the normal range. The boy's development after the seventh month is completely normal. Fetendo with urethral stent application for obstructive uropathy should be performed for the carefully selected patient with oligohydramnion and normal kidney appearance.

Adult↗

Cellular fibronectin in patients with transitional cell carcinoma of the bladder.

Various tumor markers for transitional cell carcinoma (TCC) of the bladder have been described, but none of them are used in clinical routine. Fibronectin, a glycoprotein, seems to play a very important role in both the progression and invasion of cancer. The aim of this study was to evaluate cellular fibronectin (cFN) in the urine and blood of patients with TCC of the bladder and to determine its possible role as a tumor marker and prognostic factor. Morning urine samples and blood were collected from 20 patients (8 women, 12 men, mean age 69.9 years) before they underwent transurethral resection of bladder tumors (TURB). Twenty patients (10 women, 10 men, mean age 63.4 years) with nonmalignant urological disorders were recruited as the control group. Determination of cFN in plasma and urine was performed by using a newly developed time-resolved fluorescence immunoassay (TRFIA). Patients with nonmalignant diseases had mean cFN plasma levels of 404 ng/ml (range 181-746 ng/ml). Patients with TCC of the bladder showed significantly higher cFN plasma levels of 686 ng/ml (range 274-1999 ng/ml, p<0.05). Subdivided according to the TNM system, muscle-invasive bladder tumors (n=5) demonstrated higher cFN plasma levels (mean 944 ng/ml) than superficial bladder tumors (n=15, mean 463 ng/ml). There were no differences of plasma cFN concentrations concerning tumor grade and also no differences in urine levels between the different groups. We found a significant difference (p<0.04) of cFN plasma levels between patients with TCC of the bladder and the control group. The difference in cFN plasma levels between pTa/pT1 and >or=pT2 tumors indicates a clinically useful potential of this tumor marker for preoperative staging and postoperative follow-up. Our data underline the important but still unclear role of cFN as a tumor marker in TCC, and this will be the focus of future studies.

Aged↗

High frequency of serum DNA alterations in renal cell carcinoma detected by fluorescent microsatellite analysis.

To date there are no reliable serological markers for renal cell carcinoma (RCC). We applied fluorescent microsatellite analysis (MSA) to detect serum DNA alterations in patients with RCC. Fresh tumour, peripheral blood and serum specimens from 60 consecutive patients treated for malignant renal tumours (n= 53 RCC and n= 7 non-RCC) were prospectively collected. After DNA extraction, we performed MSA with a total of 9 markers from the chromosomal regions 3p, 5q, 7p, 7q, 9p, 13q, 17p and 17q to identify tumour specific serum DNA alterations in Group I (n= 53 RCC); 11 additional markers were used in the first 23 RCCs (Group II) in order to increase sensitivity; and 20 healthy controls were investigated with 10 markers. Besides the histomorphological diagnosis the RCCs were genetically stratified according to the "Heidelberg Classification" of renal tumours. Detection of allelic imbalance and loss of heterozygosity (LOH) was carried out on an automated laser sequencer. In Group I we identified serum DNA alterations in 74% (39/53) of cases. When applying 20 markers, the sensitivity was elevated to 87% (20/23) in Group II. Investigating 20 healthy controls with 10 markers, the method rendered 85% specificity. The highest incidence of alterations was detected for chromosomal regions 3p and 5q. The presence of serum DNA alteration was not associated with tumour nuclear grade but exhibited a trend towards advanced stages (p = 0,044). In RCC, the microsatellite analysis has a high sensitivity in the detection of serum DNA alterations when a sufficient number of markers from various chromosomal regions are used. Advanced tumours tend to express serum DNA alterations more frequently.

Adenoma, Chromophobe↗

TGF-beta1 in patients with renal cell carcinoma.

Up to now, clinical tumor-markers for renal cell carcinoma (RCC) have been lacking. Increased plasma levels of transforming growth factor-beta1 (TGF-beta1) were described as a tumor-marker and prognostic factor in RCC. The aim of this study was to test the clinical suitability of plasma TGF-beta1 as a tumor-marker for RCC. The concentrations of active and latent TGF-beta1 were determined in plasma of patients with localized (n = 39) and metastasised (n = 17) RCC. A newly developed, highly sensitive ELISA, which is specific for the isoform beta1, was used. Active TGF was directly measured in the EDTA plasma. To determine the amount of latent TGF-beta1, which is bound predominantly at beta2-macroglobulin, an optimized activation procedure was applied. Patients with localized RCC showed median concentrations of 16,700 ng/l (6,200-54,800 ng/l) for latent TGF-beta1. A total of 94 patients with various nonmalignant urological diseases were recruited as a control group. In comparison, this group had median concentrations of 19,900 ng/l (2,640-52,300 ng/l) for latent TGF-beta1. There was no significant difference (nonparametric Kruskal-Wallis ANOVA) between these groups. Patients with metastatic RCC showed median concentrations of 34,500 ng/l (6,800-48,960 ng/l) for latent TGF-beta1. In comparison to the localized RCC group, a statistically significant difference was found. Plasma levels after operative therapy (days 1, 5 and 10) and during follow-up without evidence of disease (2-6 months) showed no significant differences. Contrary to other study groups, our results suggest that TGF-beta1 is not a suitable tumor-marker for the diagnosis of localized RCC. In the face of higher TGF-beta1 plasma levels in metastatic disease, TGF-beta1 may be useful in the early detection of RCC recurrence or to control the success of immunochemotherapy.

Biomarkers, Tumor↗

Accuracy of frozen section examination of testicular tumors of uncertain origin.

INTRODUCTION: A total of 80-90% of all testicular masses are malignant germ cell tumors. Benign testicular lesions are recognized in approximately 10-20% enabling a testis-preserving surgery on the findings of frozen section examination (FSE). However, there are only sparse information with regard to the reliability of FSE in testicular tumors of uncertain dignity. Therefore, we retrospectively reviewed our experience concerning the reliability of FSE in primary testicular tumors by comparing each FSE result to the final diagnosis. PATIENTS AND METHODS: From 1974 to 2000, 354 patients were operated on a testicular tumor. During inguinal exploration and after clamping of the spermatic cord and appropriate dressing, a representative biopsy of the tumor was taken and sent for FSE. In case of malignancy radical orchiectomy was performed, in case of benign findings or in case of a germ cell tumor in a solitary testicle, the tumor was enucleated. Slides of FSE and the permanent sections were reviewed and compared with regard to the histological diagnosis and presence/absence of malignancy. RESULTS: Based on FSE, 317 tumors (89.5%) were found to be malignant ((100 seminomas (38.5%), 217 nonseminomas (61.5%)) and 37 tumors (10.5%) were benign (17 epidermoid cysts, 14 Leydig cell tumors, two cystadenomas, two simple cysts, two hemangiomas). Comparing FSE and definitive diagnosis, FSE correctly identified all malignant and benign lesions. There was a failure rate of 10 and 8% to differentiate seminomatous from nonseminomatous tumors and vice versa based on FSE, which, however, was irrelevant for the surgical management. Complications of the enucleations (n = 37) were: testicular atrophy in three cases, testicular hematoma in three cases, orchitis/epididymitis in one case. Not a single case disclosed a local relapse after a mean follow-up of 105 (12-240) months. CONCLUSIONS: Intraoperative FSE correctly identified all malignant and benign testicular masses including radical orchiectomy or organ-preserving surgery. Surgical management of testicular tumors based on FSE results is clinically practicable.

Adult↗

Nephron-sparing surgery for renal angiomyolipoma.

INTRODUCTION: Renal angiomyolipoma (RAML) is a benign tumor composed of varying amounts of mature adipose tissue, smooth muscle and thick-walled blood vessels. RAML tend to grow over time requiring active intervention due to serious associated complications, such as hemorrhage and pain. Although RAML is an ideal tumor for organ preservation, data concerning efficacy of nephron-sparing surgery (NSS) are sparse. The aim of the study was to evaluate the efficacy of NSS in RAML with regard to renal function, tumor recurrence and surgical feasibility. PATIENTS AND METHODS: Charts of patients with pathologically confirmed RAML were reviewed and data recorded: tumor size, associated symptoms, intraoperative blood loss, serum creatinine, follow-up data with regard to tumor recurrence and long-term renal function. A total of 28 patients were identified with RAML who underwent NSS because of tumor size > 4 cm, pain and/or to rule out malignancy due to radiographic features of uncertain interpretation. RESULTS: The median follow-up of all patients is 58 (3-114) months; median age was 55.6 (34-78) years, 24 patients were women, 4 patients were men. None of the patients developed a local recurrence. Median size of enucleated tumors was 5.5 (2.5-15) cm; indication for NSS was symptomatic tumor with hemorrhage in 4 patients (16%), prophylaxis of hemorrhage in 5 patients (20%) and radiographic features suspicious for malignancy in 16 patients (64%). In those cases, unenhanced and enhanced CT scans exhibit a hyperdense and a hypodense lesion as compared to the adjacent normal renal cortex, respectively. There were no intraoperative complications, median blood loss was 320 (50-1200) ml, none of the patients required blood transfusions. Post-operative course was uneventful in 26 patients (96%), 2 patients (7.1%) developed a urinary fistula managed by an endoluminal stent. Pre-operative serum creatinine was 0.9 (0.7-1.3) mg/dl, post-operative creatinine was 1.23 (0.7-1.5) mg/dl and serum creatinine at last follow-up was 0.95 (0.7-1.2) mg/dl. CONCLUSIONS: NSS can be performed with a high success rate in RAML when surgical management is indicated. Long-term follow-up reveals no local tumor recurrences and stable renal function even in patients with a solitary kidney.

Angiomyolipoma↗

Bilateral fine-needle administered local anaesthetic nerve block for pain control during TRUS-guided multi-core prostate biopsy: a prospective randomised trial.

INTRODUCTION: Transrectal multi-core biopsies of the prostate can cause substantial discomfort with the need for high dose systemic analgesics. In a prospective randomised trial we investigated the efficacy of fine-needle administered local anaesthesia for bilateral prostatic nerve block prior to transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS: One hundred and eight men suspected of having cancer of the prostate were randomised to receive TRUS-guided bilateral prostate nerve block prior to biopsy or not, when having no history of previous prostate biopsies (groups I and II, n=68). In group III (n=40) all patients with history of previous biopsies exclusively received local anaesthesia injection. Patients routinely underwent a 10-core biopsy regimen. For repeat biopsy 12 cores were taken. The consented patients documented pain on a visual analogue pain score. RESULTS: In the randomised groups I and II average pain score was 1.85 with versus 3.29 without periprostatic nerve block (p<0.0001). In group III the difference in pain stated for the present biopsy with local anaesthesia nerve block in comparison to the pain experienced with the previous biopsy solely under transrectal lidocaine gel was even higher (1.71 versus 4.59; p<0.0001). Pain relief was independent of the number of biopsy cores sampled. Overall cancer detection rate was 46% (50/108). CONCLUSION: Bilateral local anaesthesia nerve block prior to multi-core TRUS-guided prostate biopsy significantly reduces pain independent of the number of cores taken.

Biopsy, Needle↗

Detection of circulating tumor cells in patients with renal cell carcinoma by reverse transcriptase polymerase chain reaction for G250/MNCA-9: results of a prospective trial.

OBJECTIVES: Radical nephrectomy displays the standard procedure for patients with localized renal cell carcinoma. The transperitoneal approach is often favored compared to the retroperitoneal approach because of the early ligation of the renal vessels, thereby tumor cell shedding by manipulation of the tumor is thought to be avoided. The aim of our study was to investigate the influence of the surgical technique on intraoperative tumor cell shedding. Furthermore, we evaluated the clinical course of the patients being operated on with either method in terms of complications, postoperative recovery, and hospital stay. METHODS: A total of 55 consecutive patients with renal tumors suspicious for malignancies were evaluated for this study. Peripheral blood samples were obtained from 44 patients at admission, intraoperatively (before and after kidney removal), and before discharge. Ribonucleic acid was extracted, converted to complementary deoxyribonucleic acid, and reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for G250/MNCA-9 was performed. Data regarding the clinical course of the patients were analyzed retrospectively by reviewing patient files. RESULTS: The clinical course for patients undergoing retroperitoneal nephrectomy was statistically different compared to the transperitoneal approach group regarding operating time and duration of drains, favoring the retroperitoneal approach group. Evaluation of MNCA-9 RT-PCR revealed no difference according to operative technique, tumor-nodes-metastasis, or clinical tumor stage. Despite this result, we found positive RT-PCR signals for MNCA-9 in patients with transitional cell cancer of the renal pelvis and benign renal lesions. CONCLUSIONS: There is no clinical relevant difference between the transperitoneal and retroperitoneal approaches for radical nephrectomy. Furthermore, the retroperitoneal approach does not bear the risk of intraoperative tumor cell shedding by the handling of the tumor.

Aged↗

Plasma levels of cellular fibronectin in patients with localized and metastatic renal cell carcinoma.

Clinical markers for renal cell carcinoma (RCC) are lacking. Fibronectin is a glycoprotein that plays an important role in cellular attachment and cell spread. The aim of this study was to test the clinical suitability of cellular fibronectin (cFN) in plasma as a tumor marker for RCC and to determine a possible relationship between cFN plasma levels and stage of disease. Therefore, cFN was determined in the plasma of patients with localized (n = 40) and metastatic (n = 20) RCC using a time-resolved fluorescence immunoassay. Fifty patients with different non-malignant urological disorders were recruited as a control group. In the control group, mean cFN plasma levels amounted to 553 ng/ml. In patients with localized RCC, plasma concentrations of cFN were increased (1,295 ng/ml; p < 0.01). Patients with metastatic disease had the highest concentrations (3,842 ng/ml). Statistical analysis demonstrated a significant difference between controls, and patients with localized and metastatic RCC (p < 0.01), with a sensitivity of 80%, a specificity of 78% and a positive predictive value of 81% using a cutoff value of 540 ng/ml (receiver-operating characteristic curve analysis). These data suggest that cFN is not a realistic marker for the detection of RCC. However, elevated plasma levels in more advanced disease and an acceptable predictive value could indicate that cFN is useful as a follow-up tool in the management of RCC patients.

Aged↗

Antineoplastic effect of immunostimulatory DNA (CpG-ODN) in a murine C57-BL6/MB-49 transitional cell carcinoma model.

BACKGROUND: Intravesical BCG installation is the standard of care in the prophylaxis of recurrent intermediate and high-risk transitional cell carcinoma (TCC), but its mode of action has not yet been elucidated. However, a Th-1 biased immune response is postulated Cell culture and animal models demonstrated the efficacy of synthetic CpG-oligodeoxynucleotides (ODN) as inducer and adjuvant for a strong Th1-response. The purpose of our study was to evaluate the antineoplastic effect of locally administered CpG ODN in a subcutaneous murine bladder cancer model. MATERIALS AND METHODS: A subcutaneous murine TCC model was established in female C57/BL6 mice using the corresponding syngeneic MB49 TCC cell line. Three groups of 5 animals received a cell suspension, standardized for 1x10(6) cells/50 microl, injected s.c. into the right and left flank. Group I received 10 nmol of CpG-ODN only into the right cell depot. Group II received 10 nmol of GpC ODN. Group III served as untreated control and received only PBS. The animals were examined at various time points after injection until sacrifice on day 14. Tumor or scar tissue were excised, weighed and examined histopathologically (HE-stain). RESULTS: Tumor sizes and weights showed no side differences. The average tumor weight on day 14 was 171 mg (SD +/- 8.9), 110 mg (SD +/- 19.2) and 18 mg (SD +/- 6.1), respectively, in groups III, II and I (p<0.05). Histopathology revealed solid vital epithelial tumors in group III and reduced vital tumor mass with central necrosis and moderate mononuclear infiltration in group II. Group I showed almost complete tumor necrosis and a considerable mononuclear inflammatory response. CONCLUSION: Immunostimulatory DNA has promising antineoplastic activity in a murine subcutaneous TCC-model. The histological findings suggest an immunologically-mediated mode of action. Further investigations are necessary to elucidate the immunological response.

Adjuvants, Immunologic↗