Diagnostic value of MRI in a pelvic mass of prostatic origin: Part 2.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
Arnulf Stenzl
Publications and source records attributed to Arnulf Stenzl.
Distorted relation between mRNA copy number and corresponding major histocompatibility complex ligand density on the cell surface.
The major histocompatibility complex (MHC) presents peptides derived from degraded cellular proteins to T-cells and is thus crucial for triggering specific immune responses against viral infections or cancer. Up to now, there has been no evidence for a correlation between levels of mRNA (the "transcriptome") and the density of MHC-peptide complexes (the "MHC ligandome") on cells. Because such dependences are of intrinsic importance for the detailed understanding of translation efficiency and protein turnover and thus for systems biology in general and for tumor immunotherapy in practical application, we quantitatively analyzed the levels of mRNA and corresponding MHC ligand densities in samples of renal cell carcinomas and their autologous normal kidney tissues. Relative quantification was carried out by gene chip analysis and by stable isotope peptide labeling, respectively. In comparing more than 270 pairs of gene expression and corresponding peptide presentation ratios, we demonstrate that there is no clear correlation (r = 0.32) between mRNA levels and corresponding MHC peptide levels in renal cell carcinoma. A significant number of peptides presented predominantly on tumor or normal tissue showed no or only minor changes in mRNA expression levels. In several cases, peptides could even be identified despite the virtual absence of the respective mRNA. Thus we conclude that a majority of epitopes from tumor-associated antigens will not be found in approaches based mainly on mRNA expression studies as mRNA expression reflects a distorted picture of the situation on the cell surface as visible for T-cells.
Amino Acid Sequence↗
Closing the tract of mini-percutaneous nephrolithotomy with gelatine matrix hemostatic sealant can replace nephrostomy tube placement.
OBJECTIVES: To investigate the outcomes using gelatine matrix hemostatic sealant to close the tract after mini-percutaneous nephrolithotomy (mini-PCNL), resulting in a tubeless setting. METHODS: After complete stone removal after mini-PCNL, a double-J ureteral stent was placed in an antegrade manner. After withdrawing the 17F Amplatz sheet from the collecting system under direct vision without irrigation, the urothelium collapsed. While retracting the sheet further, the gelatine matrix hemostatic sealant was injected. The skin incision was closed with glue. An ultrasound examination was performed on the first postoperative day to exclude the presence of urine extravasation. RESULTS: Mini-PCNL was performed in 11 patients, either as a primary, small stone, single-access procedure or as a second-look mini-PCNL because of small residual fragments after extracorporeal shock wave lithotripsy. The time to seal the mini-PCNL tract through the kidney parenchyma was 2 to 5 minutes. The mean operative time was 79 minutes. In the first 5 cases, intravenous urography was performed in addition to ultrasonography and demonstrated an intact collecting system. The subsequent procedures demonstrated similar findings, with the exception of 1 case of temporary paravasation. In all other patients, the catheter was removed on the first postoperative day. Ten of 11 patients had an uneventful follow-up until removal of the double-J catheter. No major complications were observed. CONCLUSIONS: Closing the tract of the mini-PCNL with gelatine matrix hemostatic sealant is a safe and fast alternative and provides the option of discharging the patient in good condition without the commonly used nephrostomy tube.
Adult↗
Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas.
PURPOSE: To elicit a long-lasting antitumor immune response, CD8+ and CD4+ T cells should be activated. We attempted to isolate HLA-DR-presented peptides directly from dissected solid tumors, in particular from renal cell carcinoma, to identify MHC class II ligands from tumor-associated antigens (TAA) for their use in peptide-based immunotherapy. EXPERIMENTAL DESIGN: Tumor specimens were analyzed by immunohistochemical staining for their HLA class II expression. HLA class II peptides were subsequently isolated and identified by mass spectrometry. Gene expression analysis was done to detect genes overexpressed in tumor tissue. Peptides from identified TAAs were used to induce peptide-specific CD4+ T-cell responses in healthy donors and in tumor patients. RESULTS: In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system. To our surprise, we were able to isolate and characterize hundreds of class II peptides directly from primary dissected solid tumors, especially from renal cell carcinomas, and from colorectal carcinomas and transitional cell carcinomas. Infiltrating leukocytes expressed MHC class II molecules and tumor cells, very likely under the influence of IFNgamma. Our list of identified peptides contains ligands from several TAAs, including insulin-like growth factor binding protein 3 and matrix metalloproteinase 7. The latter bound promiscuously to HLA-DR molecules and were able to elicit CD4+ T-cell responses. CONCLUSIONS: Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.
Antigens, Neoplasm↗
Radical cystectomy and orthotopic bladder replacement in females.
INTRODUCTION: More than 15 years ago, several centers started to offer urethra-sparing cystectomy and orthotopic urinary diversion for female patients with bladder malignancies. Several studies have been published, outlining both the anatomical and oncological aspects of such an approach. METHODS: In this contribution, the main aspects regarding the surgical technique of cystectomy and orthotopic urinary diversion in female patients, including technical variations which have been derived over the years, are presented. RESULTS AND CONCLUSION: The video shows a detailed description of the surgical technique, and the main steps of the procedure are demonstrated in schematic drawings as well as in animations to facilitate understanding. Emphasis is given on important anatomical and physiological aspects, which have influenced the current surgical steps. Possible sequelae on oncological and functional outcome, which play an important role in the evaluation of this procedure, are also discussed.
Cystectomy↗
Investigations of urothelial cells seeded on commercially available small intestine submucosa.
OBJECTIVES: To examine adherence and viability of human urothelial cells seeded on commercially available small intestine submucosa (SIS) specimens under serum-free conditions. MATERIALS AND METHODS: Before seeding, SIS was either washed with incubation medium or coated with collagen A, fibronectin, or pronectin. A possible influence of SIS itself on the viability of urothelial cells was analysed with conditioned cell culture medium obtained by incubation of SIS for 24hours. In addition, untreated SIS and a setting without SIS were used as controls. Viability of urothelial cells was analysed with the WST-1 assay until day 9. Histology of seeded and unseeded SIS specimens was investigated after Papanicolaou staining. To demonstrate urothelial cell adherence on SIS, immunohistology was performed with a mixture of monoclonal AE1 and AE3 anticytokeratin antibodies. RESULTS: Urothelial cells seeded on SIS revealed no measurable cell viability. SIS-conditioned cell culture medium was cytotoxic for urothelial cells after 24 hours. Histology only demonstrated cell nuclei and no cytoplasm both in seeded and unseeded SIS specimens, thus indicating porcine DNA. Expression of the cell type-specific marker proteins AE1/AE3 could not be demonstrated. CONCLUSION: Since the commercially available SIS specimens used contained porcine DNA residues and demonstrated cytotoxic effects on urothelial cells, SIS is not suitable for in vitro construction of urothelial cell-matrix implants.
Cell Adhesion↗
Diagnostic value of MRI in a pelvic mass of prostatic origin.
We report on the case of a 55-year-old male with acute urinary retention, caused by a large pelvic mass. Contrast enhanced computed tomography showed a vascularized prostatic mass with calcifications. To rule out potential bladder and rectum infiltration and to optimize imaging prior to surgical exploration, an MRI examination including MR angiography and spectroscopy was performed. Clinical findings including intraoperative results are presented in this report in detail and correlated to the results of the state of the art magnetic resonance imaging.
Calcinosis↗
Immunotherapy of renal cell carcinoma.
Carcinomas of the kidney generally have a poor prognosis and respond minimally to classical radiotherapy or chemotherapy. Immunotherapy constitutes an interesting alternative to these established forms of treatment, and indeed, cytokine-based therapies have been used for many years, leading to favorable clinical responses in a small subset of patients. During the past few years, immunotherapeutical trials targeting renal cell tumor-associated antigens have also been reported, with diverse passive or active approaches using antibodies or aimed at activating tumor-directed T lymphocytes. The following review presents the results and the progress made in the field, including classical cytokine treatments, non-myeloablative stem cell transplantation and antigen specific-based trials, with special focus on T-cell studies. In consideration of the few specific molecular targets described so far for this tumor entity, current strategies which can lead to the identification of new relevant antigens will be discussed. Hopefully these will very soon contribute to an improvement in renal cell carcinoma specific immunotherapy and its evaluation.
Antigens, Neoplasm↗
Urethrovaginal fistula--a rare complication after the placement of a suburethral sling (IVS).
A sixty-year-old woman with stress urinary incontinence had undergone a placement of an IVS (Tyco Health Care UK) in another hospital in February 2003. Seventeen months after the procedure, she complained about a suppurative discharge from the vagina and a recurrent severe stress urinary incontinence. The gynecological examination revealed an erosion of the sling into the vagina and a large urethrovaginal fistula bordered by granuloma. After removal of the sling, the urethrovaginal fistula was closed using a vaginal flap. A subsequent conservative treatment regime with duloxetine and pelvic floor training improved the stress urinary incontinence to the patient's satisfaction.
Combined Modality Therapy↗
MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies.
OBJECTIVES: Repeatedly negative prostate biopsies in individuals with elevated prostate specific antigen (PSA) levels can be frustrating for both the patient and the urologist. This study was performed to investigate if magnetic resonance imaging (MRI)-guided transrectal biopsy increases diagnostic performance in individuals with elevated or increasing PSA levels after previous negative conventional transrectal ultrasound (TRUS)-guided biopsies. METHODS: 27 consecutive men with a PSA >4 ng/ml and/or suspicious finding on digital rectal examination, suspicious MRI findings, and at least one prior negative prostate biopsy were included. Median age was 66 years (mean, 64.5+/-6.8); median PSA was 10.2 ng/ml (mean, 11.3+/-5.5). MRI-guided biopsy was performed with a closed unit at 1.5 Tesla, an MRI-compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun. RESULTS: Median prostate volume was 37.4 cm3 (mean, 48.4+/-31.5); median volume of tumor suspicious areas on T2w MR images was 0.83 cm3 (mean, 0.99+/-0.78). The mean number of obtained cores per patient was 5.22+/-1.45 (median, 5; range, 2-8). Prostate cancer was detected in 55.5% (15 of 27) of the men. MRI-guided biopsy could be performed without complications in all cases. CONCLUSION: According to our knowledge, this is the largest cohort of consecutive men to be examined by MRI-guided transrectal biopsy of the prostate in this setting. The method is safe, can be useful to select suspicious areas in the prostate, and has the potential to improve cancer detection rate in men with previous negative TRUS-biopsies.
Biopsy↗
Size does matter: 1.5 Fr. stone baskets almost double irrigation flow during flexible ureteroscopy compared to 1.9 Fr. stone baskets.
With a new generation of flexible ureterorenoscopes, a new area in stone management is emerging. Limitation of vision with these new instruments is often caused by insufficient irrigation flow, especially when using instruments like stone baskets, resulting from partial obstruction of the working and irrigation channel with these instruments. Empirically, new available smaller stone baskets seem to dramatically improve irrigation and therefore vision in clinical use. The goal of this study was to show objective differences in basket diameters and flow rates in an in vitro setting. Diameters and irrigation flows in flexible ureterorenoscopes depending on different sizes of stone baskets (Fr. 1.5-1.7-1.9-2.2-2.4-3.0) and different deflections were measured. The measured diameter of the baskets varied within the first 20 cm and the true measured size varied from the manufacturer's specified size to a different extent. The new generation of 1.5 and 1.7 Fr. baskets improved irrigation flow, even compared to the smallest commonly used baskets, up to 68%. Interestingly, deflection did not influence irrigation flow. This study confirmed the subjective impression of inadequate description of relevant basket diameters as well as that of a significant improvement of irrigation flow with the newest generation of stone baskets with smaller diameters.
Calibration↗
Comparison of flexible grasping forceps and stone basket for removal of retracted ureteral stents.
BACKGROUND: Ureteral-stent dislocation can occur either during positioning or postoperatively. Grasping the distal end of the stent and removing it depends on the angulation between the extraction device and the stent, the size and length of the instrument, and the force of the branches and resistance of the dislocated stent. PATIENTS AND METHODS: Six cases of challenging stent removal are presented, and details of the surgical technique are described. By in-vitro testing, we investigated the deflection of flexible cystoscopes and ureteroscopes using forceps or a four-wire stone basket, the ability to grasp a stent depending on the angle between the stent axis and the extraction device, and the force that can be applied on the stent with the different devices. RESULTS: In all cases, it was possible to extract the stent with a stone basket. In an in-vitro setting, maximum extraction forces, measured with a macro scale, were 1.3 kg (cystoscopic forceps) and 0.4 kg (ureteroscopic forceps) until the forceps slipped off the stent. In the same setting, a rupture of the wires of the 1.9F stone basket occurred at 0.8 kg, whereas with a 2.4F basket, a force of 1.9 kg led to rupture of the stent, leaving the basket intact. CONCLUSIONS: Using a stone basket instead of grasping forceps in difficult cases of dislocated stents opens new possibilities for their cystoscopic and ureteroscopic removal. Because the superiority of the basket is counterbalanced by its higher costs, we suggest the basket extraction method only in difficult cases.
Adult↗
Introducing a novel technique to remove accidentally stitched or entrapped urethral catheters after radical prostatectomy.
INTRODUCTION: A crucial step during radical prostatectomy is anastomosing the bladder neck to the urethral stump after specimen removal. For this purpose, a Foley catheter is inserted transurethrally to achieve a patent and watertight anastomosis. The catheter should be removed 6-10 days after the procedure to avoid ascending infection and stricture formation. On occasion, catheter removal is not possible due to fixation by one of the anastomotic sutures. In this case, a longer catheterization period may increase the risk of infection and formation of an anastomotic stricture. MATERIALS AND METHODS: In the present report, we suggest a technique to overcome this problem by using an endoscopic laser dissection of the anastomotic suture. In 2 patients, a 4.8-Fr pediatric ureteroscope was passed through the urethra along the fixated catheter. After carefully inspecting the anastomosis, a laser fiber was brought in direct contact with the responsible suture. RESULTS AND CONCLUSIONS: By activating the laser, the suture was cut immediately, and the catheter could be removed. Both patients showed no signs of anastomotic leakage or stricture on cystography. Fixation of the catheter after radical prostatectomy is a rare, but bothersome complication, which can compromise the functional outcome of the procedure. Using a pediatric ureteroscope and a laser fiber is an elegant, minimally invasive method to solve this problem. It can be easily and safely performed under local anesthesia in an outpatient setting.
Adenocarcinoma↗
Clinical outcome after cystectomy in patients with lymph node-positive bladder cancer.
Whereas radical cystectomy is the standard of care in high-grade, invasive bladder tumors, the extent of lymphadenectomy and its diagnostic and/or therapeutic potential is controversial. Independent predictors for lymph node involvement are T-stage, histological grading and lymphovascular invasion. Preoperative assessment, including 3D magnetic resonance imaging and sentinel node detection, are promising concepts for the future. The extension of lymphadenectomy is not yet defined, although prospective data regarding the absence of skipped lesions in the case of pelvic lymphadenectomy and the damage of autonomic nerves in the case of extensive lymphadenectomy are arguments for a limited or stepwise approach. Outcome of N1 patients appears to be nearly equivalent to N0 patients in organ-confined tumors, whereas the outcome of N3 patients is poor in all studies presented to date. Therefore, it has been suggested that a meticulous lymphadenectomy in N1 patients, with positive lymph nodes almost exclusively localized within the endopelvic region, has a long-term therapeutic impact in terms of an improvement in the patient's clinical prognosis. For N2 patients, a long-term survival benefit from extensive lymphadenectomy remains to be demonstrated. Recognizing the inevitably poor clinical prognosis in cases with gross nodal involvement (N3), the clinical value of an extended lymph node dissection in these patients is very questionable.
Cystectomy↗
Advances in the treatment of testicular cancer.
Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm". Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%. Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients. In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT. This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%). However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied. For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.
Antineoplastic Combined Chemotherapy Protocols↗
Activation of the PKB/Akt pathway in histological benign prostatic tissue adjacent to the primary malignant lesions.
In order to evaluate the molecular heterogeneity of prostate cancer, this study examined the expression of Akt-pathway related parameters within the cancerous prostate gland. PTEN, p-Akt and p27kip1 are known to be altered in prostate cancer. Tissue samples from malignant, tumor adjacent benign and benign areas of 25 whole mounted prostate cancer specimens were processed to 583 tissue microarray cores. Immunohistochemically determined biomarker expression was correlated to the different localizations. p-Akt and p27kip1 showed increased staining in malignant tissue compared to the respective benign tissue (p < 0.01 and p < 0.05). The adjacent but histologically benign tissue had increased levels (p < 0.05 and p < 0.01), whereas no significant difference was found between the adjacent and malignant regions. A highly significant correlation of p-Akt and p27kip1 in benign tissue (p < 0.001) was lost in the adjacent areas and in the malignant tissue (p = 0.054 and p = 0.12). In tendency, PTEN expression was decreased in the malignant regions and revealed the highest staining in the adjacent zone. According to the results obtained, the expression of p-Akt and p27kip1 was increased in both the adjacent microscopically benign tissue as well as the primary tumors when compared with the histologically benign tissue specimens that served as biological control. The increased expression of PTEN indicates its regulatory function in the initial steps of a deteriorated cell cycle control as well as uncontrolled cellular proliferation, for example, which seem to be present in the normal prostatic tissue surrounding the primary malignant lesion. The addition of molecular markers to a 'classical' histopathological approach might contribute to an enhanced sensitivity of analytical approaches aimed at the detection of malignant or premalignant lesions within prostatic biopsies.
Aged↗
Laparoscopic sentinel lymph node dissection--a novel technique for the staging of prostate cancer.
OBJECTIVES: Pelvic lymph node metastases indicate a poor prognosis for prostate cancer patients. The aim of this study was to evaluate the suitability of laparoscopic radioisotope guided sentinel lymph node (SLN) dissection in staging of prostate carcinoma. METHODS: 28 patients with prostate cancer and intermediate or high risk for lymph node metastases considered for external beam radiotherapy underwent laparoscopic pelvic lymphadenectomy at our institution. For visualization of individual SLN distribution, an image fusion system consisting of a gamma-camera with integrated X-ray tube was used. During laparoscopic lymphadenectomy, SLN were identified using a laparoscopic gamma probe. RESULTS: Preoperative imaging and laparoscopic gamma probe allowed an excellent delineation of SLN. 57% (preoperative imaging) as well as 48% (intraoperative measurements) of SLN were found outside the obturator fossa. All SLN were removed successfully without intra- or postoperative complications. Despite extended lymphadenectomy, no significant lymphocele appeared. 10 lymph node metastases were found in 7 out of the 31 patients (23%) with 3 of the 10 metastases lying outside the obturator fossa representing the standard lymphadenectomy area. CONCLUSIONS: The present data demonstrate that laparoscopic SLN dissection is an excellent minimally invasive and technically feasible tool for staging of intermediate and high risk prostate cancer.
Aged↗
MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue.
MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.
Antigens, Neoplasm↗