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Biomedical subjects

J E Gschwend

Publications and source records attributed to J E Gschwend.

At least 19 recordsLinked to original sources
PubMed2007

[Palliative and supportive treatment options in patients with advanced prostate cancer].

In patients with advanced prostate cancer, quality of life and prevention of complications come to the fore. Besides handling local complications such as obstruction, hematuria and lymphedema, treatment of bone metastases and their complications is of great importance. Analgesic measures, bisphosphonates, radiation therapy, radionuclide therapy and neurosurgical procedures are available. Spinal cord compression with acute motor and sensory deficiency requires immediate neurosurgical and/or radiation therapy. Tumor anemia should be treated appropriately.

Humans↗
PubMed2006

[Delta(9)-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain].

BACKGROUND: It is concluded from animal experiments that cannabinoid receptor and mu-opioid receptor agonists act synergistically with respect to antinociception. In order to demonstrate this effect under clinical conditions, we conducted a randomized double blind trial with patients after radical prostatectomy. PATIENTS AND METHODS: From the evening before the operation until the morning of the second postoperative day, all patients received eight oral doses of either placebo or 5 mg Delta(9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the micro-opioid agonist piritramide for 48 h. We expected patients receiving dronabinol to require significantly less piritramide compared to patients on placebo. RESULTS: The consumption of piritramide was recorded in 100 patients after radical retropubic prostatectomy with regional lymphadenectomy. Patients in the placebo group consumed 74 mg (median), interquartile range (IQR) 44-90 mg, patients in the verum group consumed 54 mg (median) IQR 46-88 mg. The difference between groups was not statistically significant. Plasma concentrations of Delta(9)-THC were measurable in all patients in the verum group. The levels (median) were 1.5 ng/ml (IQR 0.6-2.3), 1.3 ng/ml (IQR 0.5-2.2) and 1.9 ng/ml (IQR 0.8-2.7) on the day of operation, the first and second postoperative day, respectively. CONCLUSION: We found neither a synergistic nor even an additive antinociceptive interaction between Delta(9)-tetrahydrocannabinol and the micro-opioid agonist piritramide in a setting of acute postoperative pain.

Aged↗
PubMed2006

[Management of erectile dysfunction after radical prostatectomy. Urologists' assessment vs patient survey responses].

INTRODUCTION: The aim of this national study was to evaluate ED management after RPX (without any postoperative adjuvant therapy or tumor relapse) from the patient's view compared to the urologist's view. MATERIAL AND METHODS: In May 2003 we queried 1063 urologists and 801 patients following radical prostatectomy without adjuvant therapy. They were asked about preserved potency without erectile aid, existing wish for ED therapy, recommended or tested erectile aid (oral, transurethral, intracorporal, vacuum constriction device[VCD], penile implant) as well as the long-term use. Return rate: patients 80.1%, urologists 26.7%. RESULTS: According to the urologists' view 9.1% of their affected patients were potent postoperatively without a device, but according to the polled patients only 4.7%. The wish to be treated for erectile dysfunction existed in the urologists' opinion in 46.1% of their patients, while they considered that 44.8% had no wish for treatment. On the other hand, 59.3% of the patients would like to be treated and only 28.5% did not want any kind of treatment. Regarding the long-term use of therapy for ED, the urologists thought that 26.1% of their patients did not receive therapy for the problem, and 69.7% of the patients stated they received no long-term therapy. Only 30.3% of the patients confirmed long-term therapy, while the urologists thought that 73.9% of the patients used an erectile aid. Definite therapy in the urologists' opinion involved: oral medication in 38.4%, MUSE in 3.6%, (SKAT) in 37.3%, VCD in 20.4%, and a prosthesis in 0.3%. Indeed 19.8% of the patients used oral medication, 1.7% MUSE, 26.7% SKAT, 50.9% VCD, and 0.9% penile implant. Considering the satisfaction of patients, urologists thought that 46.2% of the patients were satisfied with their treatment of ED, but only 28.9% of the patients were actually satisfied themselves. CONCLUSIONS: The comparison of patients' and urologists' views shows a clearly different description of the ED situation after RPX. The proportion of patients with a wish for treatment and the proportion of dissatisfied patients are much higher from the patients' view. This demonstrates an undertreatment of ED patients after RPX, which should also be taken into account under the current changes in the German health care system.

Cross-Sectional Studies↗
PubMed2006

[Systemic therapy of metastatic renal cell carcinoma].

Cytokine-based immunotherapy was the only viable option in metastatic, nonresectable renal cell carcinoma (RCC) for many years. Systemic immunotherapy has become increasingly established as a standard therapy during the last 15 years. In this context, interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) turned out to be the most effective single agents in RCC. Subsequently, the approved subcutaneous application of these compounds was the preferred administration route in Germany. Response rates with cytokine combination therapy were almost similar to those of more aggressive concepts using additional chemotherapeutic agents.Currently, new compounds targeting specific signaling pathways are readily available and have passed clinical testing. Such small molecules like tyrosine kinase inhibitors, monoclonal antibodies, or the mTOR inhibitor CCI-779 may dramatically change the established concepts of systemic RCC treatment. This paper gives an overview of established, current, and evolving concepts of systemic therapy in RCC.

Antibodies, Monoclonal↗
PubMed2006

[Prospective evaluation of prostate cancer screening in men with a family history of the disease].

BACKGROUND: Family history is one of the strongest risk factors for prostate cancer. In this prospective study we evaluated the results of prostate cancer screening performed in healthy brothers of prostate cancer patients. The detection rate of prostate cancer and the positive predictive value of the examinations were determined. MATERIAL AND METHODS: The study population comprised 513 healthy men who were 38-75 years of age (median 62.0 years). Of these men, 268 having only one affected brother with prostate cancer were assigned to the sporadic group, and 245 probands having 2-10 affected relatives were assigned to the familial group. An abnormal PSA and/or a pathological digital rectal examination (DRE) was noted in 17.5% of familial (43/245) and 15.8% of sporadic probands (35/268). A biopsy of the prostate was performed in 60.5% of familial (26/43) and 71.4% of sporadic (25/35) men with pathological findings. RESULTS: Prostate cancer was found in 15 of 26 familial (57.7%) and 16 of 25 sporadic (64.0%) probands by prostate biopsy. The overall detection rate was 6.0% (31/513). CONCLUSION: Due to an increased prevalence the detection rate of prostate cancer and the positive predictive value of PSA and/or DRE are higher in men with a family history as expected in an unselected population. Our data suggest that in predisposed men prostate cancer screening should be recommended early. Furthermore an early indication for prostate biopsy is necessary. This recommendation should also be applied if only one first-degree relative has prostate cancer.

Adult↗
PubMed2006

[Association of a positive family history with histopathology and clinical course in early-onset prostate cancer].

BACKGROUND: In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS: The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS: The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS: Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.

Aged↗
PubMed2006

Neobladder emptying failure in males: incidence, etiology and therapeutic options.

PURPOSE: Neobladder reconstruction is considered the best option for patients requiring cystectomy. Limited information is available about incidence, etiology and therapeutic options for neobladder emptying failure in males. MATERIALS AND METHODS: In a retrospective study we analyzed the data of a consecutive series of 655 male patients (age range 23 to 82 years, median 63; followup range 0 to 208 months, median 36.5) who received an ileal neobladder following radical cystectomy at our institution. All patients had a complete followup until death or until December 2003. Data on all diagnostic and therapeutic procedures performed for neobladder emptying failure were collected. RESULTS: Of 655 patients 75 (11.5%) had at least 1 episode of failure emptying the neobladder requiring some form of therapy during followup. Failure was due to dysfunctional voiding in 23 patients (3.5%) and mechanical obstruction in 52 patients (8%). Causes of mechanical obstruction were benign strictures of the neovesicourethral anastomosis (23 patients, 3.5%) or the anterior urethra (11 patients, 1.7%), neoplastic obstruction by local tumor recurrence (13 patients, 2.0%) or a nonurological malignancy (1 patient, 0.2%), and obstruction by mucosal valves (3 patients, 0.5%) or a foreign body (1 patient, 0.2%). In 38 of 52 patients with mechanical obstruction of the neobladder outlet emptying was fully restored with endourological procedures, while in 14 of 52 patients long-term catheterization was necessary. Catheterization was the therapy of choice for all patients with dysfunctional voiding. CONCLUSIONS: Neobladder emptying failure is of major concern but is not an argument against orthotopic diversion. The overall rate of transient or permanent neobladder emptying failure in males is high but most of the mechanical causes can be managed endoscopically, while the rate of patients with long-term catheterization for dysfunctional voiding is relatively low.

Adult↗
PubMed2005

Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer.

In prostate cancer, biomarkers may provide additional value above standard clinical and pathology parameters to predict outcome after specific therapy. The purpose of this study is to evaluate an 80 kDa fragment of the cell adhesion molecule e-cadherin as a serum biomarker. A broad spectrum of prostate cancer serum samples, representing different stages of prostate cancer disease, including benign prostatic hyperplasia (BPH), localised (Loc PCA) and metastatic prostate cancer (Met PCA), was examined for the cleaved product. There is a significant difference in the expression level of the 80 kDa fragment in the serum of healthy individuals vs patients with BPH and between BPH vs Loc PCA and Met PCA (P<0.001). Highest expression levels are observed in advanced metastatic disease. In the cohort of Loc PCA cases, there was no association between the 80 kDa serum concentration and clinical parameters. Interestingly, patients with an 80 kDa level of >7.9 microg l(-1) at the time of diagnosis have a 55-fold higher risk of biochemical failure after surgery compared to those with lower levels. This is the first report of the application of an 80 kDa fragment of e-cadherin as a serum biomarker in a broad spectrum of prostate cancer cases. At an optimised cutoff, high expression at the time of diagnosis is associated with a significantly increased risk of biochemical failure, potentially supporting its use for a tailored follow-up protocol for those patients.

Aged↗
PubMed2005

[Is the prostate cancer screening behaviour of men with familial predisposition predictable?].

Little is known about the motives of German men to attend or refuse preventive checkups for prostate cancer. The aims of this study were to investigate if in men with familial predisposition screening behaviours are influenced by epidemiological or clinical parameters of prostate cancer of their affected relatives. 476 probands with one and 312 probands with at least two affected relatives were advised in writing to have a PSA-test and DRE done at their local urologists. We evaluated if the response rate was correlated to the proband's age, to the number and the age of onset of their affected relatives and also to the clinical course of their disease. Our data implicate that in men with familial predisposition the acceptance of prostate cancer screening is influenced only by individual characteristics and personal attitude and not by factors within the family. To which extent the awareness of disease risk is modified by familial predisposition remains to be evaluated.

Adult↗
PubMed2005

[Local recurrence following radical cystectomy for bladder cancer. Diagnostic and therapeutic options].

The prognosis for patients with local recurrence following cystectomy for urothelial bladder cancer is poor. Only a small proportion of patients with good performance status are candidates for any form of therapy at all. Clinical experience shows that local recurrence is often accompanied or followed by systemic tumor spread. Therefore, palliative systemic chemotherapy is the cornerstone of treatment. Local radiotherapy or local tumor resection is reserved for subgroups of patients and to ease local symptoms or complications. Only a few patients are candidates for multimodal therapeutic approaches with curative intent. Despite such efforts, the survival of patients with local recurrence is limited in nearly all cases.

Antineoplastic Agents↗
PubMed2004

[Rational therapy of urolithiasis in every-day practice].

Patients with renal colic are usually treated in emergency care units or by their family doctors and require immediate diagnosis and treatment. The life-time risk is up to 10 %. The prevalence amounts to 4.7 % in Germany. In addition to confirming the diagnosis and inducing an adequate pain therapy it's very important for patients to be directed correctly and, above all, prevention is important, too. Without treatment the recurrence rate ranges between 50 and 100 %. Particularly, these principals should give useful advice, wherever patients are treated without urological department.

Analgesics↗
PubMed2004

[Rational diagnosis of urolithiasis in daily practice].

Patients with renal colic are usually treated in emergency care units or by their family doctors and require immediate diagnosis and treatment. The life-time risk is up to 10 %. The prevalence amounts to 4.7 % in Germany. In addition to confirming the diagnosis and inducing an adequate pain therapy it is very important for patients to be directed correctly and, above all, prevention is important, too. Without treatment the recurrence rate ranges between 50 and 100 %. Particularly, these principals should give useful advice, wherever patients are treated without urological department.

Adult↗
PubMed2004

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer.

Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and c-myc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21-Rb-c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

Administration, Oral↗
PubMed2004

[Tissue microarrays. High-throughput procedures to verify potential biomarkers].

High-throughput molecular screening tools have created a need for equally rapid means to verify potential biomarkers. Tissue microarray (TMA) technology facilitates effective analysis on the protein level. Hundreds of 0.6-mm-diameter tissue samples are placed on a single standard glass slide. This approach allows analysis with different in situ methods of all tissue samples in one experiment under standardized conditions. TMAs are not only perfectly suited for molecular epidemiologic studies if applied on multitumor arrays composed of a variety of tumor entities, but they are also used for tumor-specific investigations of molecular markers. In this report the technical aspects of TMAs as a miniaturized high-throughput technology are described. We further demonstrate how the TMA technique will help to accelerate the transition from basic research to clinical application in prostate cancer disease.

Biomarkers, Tumor↗
PubMed2004

[Radical cystectomy and urinary diversion in elderly patients with increased comorbidity].

Radical cystectomy with urinary diversion is the accepted standard of care for invasive bladder cancer with orthotopic neobladders. It is the preferred method for bladder substitution in male and female patients and even in selected patients with locally advanced tumors. The complication rates for orthotopic bladder substitutes are similar to or lower than the morbidity rates after conduit formation or continent cutaneous diversion. Due to progress in perioperative management, intensive care and surgery, cystectomy is now part of the classical treatment options for bladder cancer in elderly patients, with acceptable morbidity rates. However, the indication for cystectomy in people older than 75 years should be based on a rigorous preoperative risk assessment (ASA status) and a life expectancy of more than 2 years independent of the tumor. Transurethral resection alone should be proposed only to patients with a poor performance status.

Aged↗
PubMed2004

Comparison of external radiation therapy vs radical prostatectomy in lymph node positive prostate cancer patients.

INTRODUCTION: Treatment options for lymph node positive prostate cancer are limited. We retrospectively compared patients who underwent external radiotherapy (ERT) to patients treated by radical prostatectomy (RPX). MATERIALS AND METHODS: A total of 102 lymph node positive patients from the RPX series at Ulm University were evaluated. In all, 76 patients received adjuvant androgen withdrawal as part of their primary treatment. In the ERT group, 44 patients were treated at the University of Michigan using a fractionated regimen. Of these, 21 patients received early adjuvant hormonal therapy. Patients with neoadjuvant therapy before RPX or ERT were excluded. RESULTS: In the RPX group, PSA nadir (nadir < or = 0.2 vs > 0.2 ng/ml) showed a strong association with outcome. In the ERT group, pretreatment PSA was an independent predictor of outcome (P = 0.04) and patients with adjuvant hormonal therapy had a significant longer recurrence-free interval compared to patients without adjuvant therapy (P = 0.004). Comparing only patients with adjuvant hormonal treatment after cancer-specific therapy, the ERT-treated patients had a borderline longer PSA recurrence-free survival time compared to the RPX-treated patients (P = 0.05). CONCLUSIONS: In case of positive lymph nodes, RPX and ERT might be considered and need to be explained to the patient. For future treatment decisions, the presented findings and a potential survival benefit need to be evaluated in a larger prospective setting.

Aged↗