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Biomedical subjects

Georg Bartsch

Publications and source records attributed to Georg Bartsch.

175 records · Page 10Linked to original sources
PubMed2002

The remnant urothelium after reconstructive bladder surgery.

The pathology of the remnant urinary tract in an increasing population of cystectomy patients with orthotopic and heterotopic bladder substitution due to primary bladder carcinoma, and its management is discussed. The incidence of urethral tumours in primary or recurrent bladder cancer in long-term studies is approximately 6% for male and 2% for female patients. Risk factors for urethral tumour occurrence are tumours at the bladder neck and recurrent multifocal tumours. CIS of the bladder not involving the bladder neck, and muscle invasive tumours with or without lymph node involvement are not significantly correlated with urethral cancer. Those patients at risk for urethral tumours need additional work-up (multiple urethral biopsies and/or urethral brushings, frozen section of the membranous urethra) before an orthotopic lower urinary tract reconstruction to the urethra should be considered. In a large series of male patients, the majority of patients with urethral tumours had a single conservative treatment session, and did not recur thereafter demonstrating the feasibility of a conservative approach for superficial urethral tumour recurrences in patients with an orthotopic neo-bladder to the urethra. The incidence of upper tract tumours following cystectomy and lower urinary tract reconstruction lies between 2.4-17%. In a group of 258 patients with an orthotopic bladder substitution, we have seen an incidence of 3.5%. Tumour multifocality, carcinoma in situ in the bladder and/or distal ureter, locally advanced bladder tumour stage, and invasion of the intramural ureter were seen as risk factors in some series. A tendency for a higher incidence can be seen in those series with longer follow-up. The median time between cystectomy and diagnosis of upper tract tumours lies between 8 and 69 months in most series. A longer observation period in larger numbers of patients with an orthotopic neo-bladder and longer survival rates in general after cystectomy may reveal an increase in the incidence of upper tract tumours over the next decade.

Carcinoma, Transitional Cell↗
PubMed2002

Microsatellite alterations in human bladder cancer: detection of tumor cells in urine sediment and tumor tissue.

OBJECTIVES: Bladder cancer is the result of clonal expansion of cancer cells in which multiple genetic alterations have occurred. Loss of heterozygosity (LOH) studies have demonstrated that alterations in microsatellite regions are common in bladder cancer. This observation offers the possibility of early tumor detection by examining the DNA of urinary sediment. METHODS: We investigated alterations of 17 microsatellite loci in urinary bladder carcinomas of different stages and grades. Per locus, 19-30 specimens were evaluated. DNA was isolated from tumor specimens, urinary sediment and peripheral blood lymphocytes. DNA fragments of 17 microsatellite loci were amplified by PCR and analyzed for genomic alterations. RESULTS: Microsatellite alterations were detected in tumor tissue and urine sediment from 27 out of 31 patients (87%). Urine sediment analysis alone proved positive in 24 out of 31 patients (77%). The type of lesions most frequently detected was LOH (74% of all alterations), followed by length alteration (24%) and additional alleles (2%). On average, the alteration frequency was 22% per locus. The loci at chromosomes 9 and 18 proved most informative. No alterations were found in grade I tumors. The study revealed a correlation between microsatellite alterations and the respective grades and stages of the tumors. Average alteration frequencies per locus were: 27.4% in grade III versus 19.3% in grade II tumors, 26.5% in invasive versus 12.3% in superficial tumors. CONCLUSIONS: Our results demonstrate that microsatellite alterations are common in bladder cancer and that analysis of genomic instabilities in urine samples should be further evaluated as a method for bladder cancer screening in a high-risk group. Especially, when a set of microsatellites is used that shows a high probability of detecting alterations and allows easy handling, this could be an alternative or a completion to currently available methods.

Carcinoma, Transitional Cell↗
PubMed2002

Blunt renal trauma in children: 26 years clinical experience in an alpine region.

OBJECTIVES: From 1975 to 2001, 254 children aged younger than 17 were transferred to our department for renal trauma. We performed a retrospective study to assess causality and kind of the trauma, diagnostic procedures and therapeutic consequences, respectively. METHODS: The 254 children at a mean age of 10.56 years (+/-3.8) ranging from 2 to 17 years were treated for kidney trauma. Among these, 166 presented with a grade I trauma according to the kidney injury scale of the American Association for the Surgery of Trauma without any other accompanying injuries and 88 had a grade II-V lesion, respectively. Diagnostic evaluation included various standard lab tests such as urinalysis and routine blood parameters, ultrasound, IVP and/or CT. RESULTS: Most of the traumatic injuries resulted from skiing accidents. However, 18 children had a severe polytrauma with laceration of other vital organs. Most of the renal injuries could be treated conservatively. Surgical treatment options included immediate exploration, reconstruction, partial resection, or even nephrectomy. No child died. CONCLUSIONS: Due to leisure time activities in our region, skiing accidents often result in isolated laceration of the kidney. About one third presented with a severe kidney trauma, and approximately 20% of all affected children required surgical therapy. However, most of the injured kidneys could be preserved and only four nephrectomies had to be performed.

Accidental Falls↗
PubMed2002

A comparison of laparoscopic pyeloplasty performed with the daVinci robotic system versus standard laparoscopic techniques: initial clinical results.

PURPOSE: Laparoscopic pyeloplasty is an accepted therapy for primary ureteropelvic junction obstruction (UPJO), however difficulty associated with intracorporeal suturing has limited widespread clinical application. We report our initial experience of laparoscopic pyeloplasty performed with the daVinci robotic system matched to procedures performed with standard laparoscopic techniques. PATIENTS AND METHODS: From June 2001 until August 2001, six patients underwent definitive management of primary UPJO using the daVinci robotic system. In four patients an Anderson-Hynes pyeloplasty was performed, while in two patients Fengerplasty was performed. Using demographic and preoperative information, each patient in the daVinci-assisted group was matched to a corresponding patient with primary UPJO undergoing laparoscopic pyeloplasty with standard techniques between November 1999 and June 2001. Perioperative results and follow-up data were subsequently compared. RESULTS: Treatment groups were identical with regard to surgical procedure, gender, and side of UPJO. The length of hospitalization was 4 days for all patients, regardless of treatment group. Estimated blood loss was <50 cc in all cases. For Anderson-Hynes pyeloplasty, the mean overall operative and suturing times were 140 and 70 min using the daVinci system and 235 and 120 min using standard techniques, respectively. For the Fengerplasty, the mean overall operative and suturing times were 78 and 13 minutes using the daVinci system and 100 and 28 minutes using standard techniques, respectively. No complications were observed and there were no open conversions. CONCLUSION: Anderson-Hynes pyeloplasty and Fengerplasty are feasible using either conventional laparoscopic techniques or the daVinci robotic system. In this initial pilot study, procedures performed with the daVinci robotic system resulted in overall decreased operative time, however factors responsible for the decreased operative time remain to be defined. Long-term prospective follow-up of procedures performed with or without the daVinci robotic system for surgeons with limited experience in laparoscopic management of UPJO is warranted to delineate the true efficacy of the device.

Humans↗
PubMed2002

Inhibition of LNCaP prostate tumor growth in vivo by an antisense oligonucleotide directed against the human androgen receptor.

We have shown recently that a 15-mer phosphorothioate oligodeoxynucleotide (ODNas750/15) that hybridizes to the (CAG)n polyglutamine region of mRNA encoding human androgen receptor (AR) inhibits the expression of AR in LNCaP prostate cancer cells in vitro. This AR downregulation was accompanied by significant cell growth inhibition and reduced PSA secretion. In the present study we investigated the effects of this antisense AR ODN on prostate tumor growth in vivo using a mouse xenograft model. Via subcutaneously implanted diffusion pumps, either ODNas750/15 or a scrambled control sequence ODNsr750/15 was continuously administered into LNCaP tumor-bearing male nude mice for 7 weeks. Compared with untreated control animals, treatment with ODNas750/15 resulted in significant tumor growth inhibition. Retardation of tumor growth was also significant in castrated mice, whereas the scrambled control ODN did not exert any effects. No side effects such as loss of body weight were observed at any time of treatment. ODN treatment was well tolerated and, in contrast to castration, did not induce shrinkage of mouse prostates. Both AR expression in the tumor and PSA levels in mouse serum correlated with tumor size. However, we failed to demonstrate a correlation between tumor retardation and Ki-67 antigen expression and the number of apoptotic cells, respectively. Testing of antisense-treated LNCaP cells revealed that expression levels of other proteins that contain shorter polyglutamine sequence stretches such as HDAC2, TFIID, and c-jun were not affected. The present study demonstrates that downregulation of AR with antisense ODNas750/15 causes prostate tumor growth inhibition. These results further point out the important role of the AR in prostate tumors and support further testing of AR downregulation for treatment of prostate cancer.

Animals↗
PubMed2002

Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease.

BACKGROUND AND PURPOSE: Unilateral total adrenalectomy is the standard treatment for benign unilateral adrenal tumors. Partial adrenalectomy has to be considered for bilateral adrenal tumors. Recently, our group has reported the feasibility of unilateral and bilateral partial adrenalectomy by means of laparoscopy. Now, we present a case of recurrent pheochromocytoma after open bilateral adrenalectomy and demonstrate that laparoscopic cortex-sparing surgery is feasible for a recurrence after open surgery. CASE REPORT: At the age of 10 years, a boy was found to have bilateral adrenal pheochromocytoma and was treated by open bilateral partial adrenalectomy. Eight years later, the patient presented with palpitation, sweating, and severe hypertension. Investigations biochemically and radiologically demonstrated functional recurrent pheochromocytoma in the left adrenal gland. Genetic studies confirmed mutation of the von Hippel-Lindau (VHL) gene. The patient was prepared for surgery preoperatively by phenoxybenzamine and metropolol. The surgery was performed as planned, and the normal adrenal tissue was spared. The patient had an uneventful postoperative course. His blood pressure was normal on the day of discharge. CONCLUSIONS: In a specialized center with experienced laparoscopic surgeons, laparoscopic partial adrenalectomy for recurrent pheochromocytoma is feasible even after previous open surgery on the ipsilateral adrenal gland. Adrenal-sparing surgery is indicated in hereditary syndromes such as VHL and MEN II to avoid the problems of life-long steroid replacement. Recurrences have to be expected, but further surgery may be less difficult by the previous laparoscopic approach.

Adolescent↗
PubMed2002

Contrast enhanced reflux sonography in children: a comparison to standard radiological imaging.

PURPOSE: The diagnosis of vesicoureteral reflux is routinely performed by voiding cystourethrography. Especially in the course of conservative treatment, the radiation dose might increase during the years. With the development of ultrasound echo enhancing agents we assessed their diagnostic efficacy for evaluation of vesicoureteral reflux to replace voiding cystourethrography with radiation-free ultrasound. MATERIALS AND METHODS: A total of 104 children with a mean age of 5.4 years were examined using echo enhancing ultrasound after informed consent was obtained. For control purposes, all children underwent standard voiding cystourethrography as well. The diagnosis of vesicoureteral reflux was positive when microbubbles appeared in the ureter or renal pelvis. The sonographic findings were correlated with those obtained by standard voiding cystourethrography. RESULTS: Of the 208 ureter and renal units investigated vesicoureteral reflux was detected in 76 (37%) by both technologies. Diagnosis was made sonographically in 5 units and by voiding cystourethrography in 3. All reflux grades (I to V) could be identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 minutes combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. CONCLUSIONS: Our results clearly demonstrate that the diagnostic accuracy of vesicoureteral reflux by contrast enhanced ultrasound is statistically significant compared to standard radiological voiding cystourethrography. Therefore, this methodology represents an exceptional approach to reduce the number of children being exposed to ionizing radiation especially during conservative followup.

Adolescent↗
PubMed2002

Comparison of contrast enhanced color Doppler targeted biopsy with conventional systematic biopsy: impact on prostate cancer detection.

PURPOSE: We performed a prospective study to determine whether a limited biopsy approach with contrast enhanced color Doppler ultrasound targeted biopsy of the prostate would detect cancer as well as gray scale US guided systematic biopsy with a larger number of biopsy cores. MATERIALS AND METHODS: We examined 230 male screening volunteers with a total prostate specific antigen of 1.25 ng./ml. or greater and free-to-total prostate specific antigen less than 18%. Two independent examiners evaluated each subject and a single investigator performed 5 or fewer contrast enhanced targeted biopsies into hypervascular regions in the peripheral zone during intravenous infusion of the US contrast agent Levovist (Schering, Berlin, Germany). Subsequently another examiner performed 10 systematic prostate biopsies. The cancer detection rates of the 2 techniques were compared. RESULTS: Cancer was detected in 69 of the 230 patients (30%), including 56 (24.4%) by contrast enhanced targeted biopsy and in 52 (22.6%) by systematic biopsy. Cancer was detected by targeted biopsy alone in 17 patients (7.4%) and by systematic biopsy alone in 13 (5.6%). The overall cancer detection rate by patient was not significantly different for targeted and systematic biopsy (p = 0.58). The detection rate for targeted biopsy cores (10.4% or 118 of 1,139 cores) was significantly better than for systematic biopsy cores (5.3% or 123 of 2,300 cores, p <0.001). Contrast enhanced targeted biopsy in a patient with cancer was 2.6-fold more likely to detect prostate cancer than systematic US guided biopsy. CONCLUSIONS: Contrast enhanced color Doppler targeted biopsy detected as many cancers as systematic biopsy with fewer than half the number of biopsy cores. Although an increase in cancer detection was achieved by combining targeted and systematic techniques in this screening population, contrast enhanced targeted biopsy alone is a reasonable approach for decreasing the number of biopsy cores.

Adult↗
PubMed2002

Acquisition of agonistic properties of nonsteroidal antiandrogens after treatment with oncostatin M in prostate cancer cells.

PURPOSE: Interleukin-6 (IL-6), a proinflammatory cytokine the serum andtissue levels of which are elevated in prostate cancer patients, activates the androgen receptor (AR) in a ligand-independent and synergistic manner. Oncostatin M (OSM) is an IL-6 type cytokine that regulates the growth of prostate cancer cells in a paracrine fashion. The present study was designed to investigate the regulation of AR expression and function by OSM, as well as the efficacy of the nonsteroidal antiandrogens hydroxyflutamide and bicalutamide in the inhibition of AR-mediated signal transduction. EXPERIMENTAL DESIGN: Expression of the OSM receptor-beta in the prostate cancer cell lines LNCaP, PC-3, and DU-145 was investigated by reverse transcription-PCR. DU-145 and PC-3 cells were cotransfected with an androgen-responsive gene and AR cDNA. Reporter gene activity was measured after treatment with androgen and/or OSM in the absence or presence of antiandrogens or protein kinase inhibitors. AR expression after OSM treatment was assessed by Western blot. RESULTS: OSM receptor-beta expression was higher in DU-145 and PC-3 than in LNCaP cells. OSM caused ligand-independent activation of the AR in DU-145 cells, and the maximal activation was 62% of that induced by the synthetic androgen methyltrienolone. In the presence of OSM, hydroxyflutamide behaved as an AR agonist. Bicalutamide down-regulated AR activation caused by OSM only at a concentration of 1 microM. The inhibitor of the protein kinase A signaling pathway PKI and dn signal transducers and activators of transcription (STAT) 3 showed no effect on AR activation by OSM. The inhibitor of the MAPK pathway, PD 98059, caused only a minor down-regulation of OSM-induced reporter gene activity. OSM did not change AR expression in DU-145 cells transfected with AR cDNA. CONCLUSIONS: OSM is a member of the IL-6 family of cytokines, which causes ligand-independent activation of the AR without altering receptor expression. In contrast to AR activation by IL-6, nonsteroidal AR antagonists act as agonists in the presence of OSM. This may be attributable to recruitment of different intermediary signal transduction proteins by OSM and IL-6, respectively. The acquisition of agonistic properties of AR blockers in the presence of OSM might compromise use of these drugs in prostate cancer treatment.

Androgen Antagonists↗
PubMed2002

Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells.

PURPOSE: We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2. RESULTS: Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive. CONCLUSIONS: Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.

Adult↗
PubMedDate not supplied

Derivatized cellulose combined with MALDI-TOF MS: a new tool for serum protein profiling.

Providing a rapid and sensitive protein profiling method for biomarker discovery from a variety of biological samples is crucial for the introduction of new markers that improve cancer patient diagnosis at early tumor stages, thus increasing the chances of curative treatment. We report here the development and application of derivatized cellulose particles for selective serum protein profiling. For immobilized metal ion affinity chromatography (IMAC), cellulose was derivatized with glycidyl methacrylate (GMA) and subsequently with iminodiacetic acid (IDA). To investigate the application of this material for generating protein profiles of human serum samples, the serum samples were agitated with the derivatized cellulose particles to a suspension and incubated for 2 h at 30 degrees C. After washing, 1 microL of the IDA-Cu(2+)-cellulose suspension was applied directly onto a MALDI-target, mixed with sinapinic acid (SA) and analyzed with MALDI-TOF MS. Consistent serum specific data were obtained from aliquoted samples analyzed several times, indicating the reliability of the method. However, the serum fingerprints obtained proved to be specific for any given serum. The technique presented allows a high enrichment of sample on the developed target leading to a high sensitivity and reproducibility without depletion of albumin and immunoglobulin, and sample elution prior to MS-analysis. The study demonstrates for the first time that derivatized cellulose particles combined with MALDI-TOF MS represent a simple, economical, and rapid approach to generate serum protein profiles for biomarker identification.

Biomarkers↗
PubMedDate not supplied

Expression of bFGF, VEGF and c-met and their correlation with microvessel density and progression in prostate carcinoma.

BACKGROUND: Previously, we found angiogenesis measured as microvessel density (MVD) to be associated with both pathological stage and clinical outcome after radical prostatectomy (RP). In addition, we have shown that Vascular Endothelial Growth Factor (VEGF) is one of the important inducers of angiogenesis in prostate cancer (PC). The aim of this study was to investigate the expression of additional angiogenic factors, namely basic Fibroblast Growth Factor (hFGF) and the c-met receptor of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in PC. MATERIALS AND METHODS: Ninety-eight paraffin-embedded RP specimens and 20 adjacent normal prostatic tissues were evaluated for factor VIII staining and microvessel counting. Expression of VEGF (n=55), bFGF (n=65) and c-met (n=66) was studied by immunohistochemistry. Results were correlated with pathological grade and stage, MVD and clinical outcome. RESULTS: While adjacent benign tissue in RP specimens generally showed low MVD, VEGF-, bFGF- and c-met-expression, this was different in PC. All angiogenesis inducers were associated with stage while c-met as well as VEGF expression were associated with grade. Tumor progression was associated with grade and MVD. There was a clear correlation between VEGF and c-met expression and MVD. CONCLUSION: VEGF and c-met expression increase with tumor stage and grade, while bFGF expression increases only with tumor stage. In addition to VEGF, c-met seems to be important and clinically relevant to the induction of angiogenesis in PC. Both VEGF and c-met appear to influence tumor progression, mainly through their effect on MVD.

Factor VIII↗