Finite element analysis of the influence of interdigitation pattern and collagen fibers on the mechanical behavior of the midpalatal suture.

The midpalatal suture (MPS) corresponds to the tissue that joins the two maxillary bones. Understanding the mechanical behavior of this tissue is of particular interest to those patients who require orthodontic treatments such as Rapid Maxillary Expansion (RME). The objective of this research was to observe the influence of interdigitation and collagen fibers on the mechanical response of MPS. To this end, a finite element analysis in two-dimensional models of the bone-suture-bone interface was performed considering the characteristics of the MPS. The geometry of the suture was modeled with 4 different levels of interdigitation: null, moderate, scalloped and fractal. The influence of collagen fibers, aligned transversely along the suture, was considered by incorporating linked structures of the bone fronts. According to the results, the factor that has the greatest impact on the magnitude and distribution of stresses is the interdigitation degree. A higher level of interdigitation produces an increase in tissue stiffness and a lower influence of collagen fibers on the mechanical response of the tissue. Therefore, this research contributes to the understanding of the MPS biomechanics by providing information that may be useful to health staff when evaluating the feasibility of procedures such as RME.

[Closure of persisting rectourethral fistula after suprasymphyseal adenoma enucleation of the prostate by combining the Bressel-Naujox and gracilis flap procedure]. / Verschluss einer persistierenden urethrorektalen Fistel nach suprasymphysärer Adenomenukleation der Prostata durch kombiniertes Bressel-Naujox- mit einem Gracilisflapverfahren.

When taking into consideration the basic principles of fistula surgery, numerous options are available for the surgical repair of rectourethral fistulas. However, there is no standard regarding which surgical method should be used under which circumstances-due to the heterogeneity of this disease. This case report describes the individual adaptation of a surgical technique that is used for the treatment of vesicovaginal fistulas to treat a rectourethral fistula in a patient who had already undergone an unsuccessful fistula closure attempt. Successful closure of the fistula was achieved on the basis of an established method using tissue interposition.

The concentration of console surgeons: prospective evaluation of the loss of attention in robotic-assisted procedures.

To prospectively evaluate the possible loss of attention among console surgeons performing robotic-assisted procedures using a validated psychological test. The concentration of one console surgeon was assessed before and after 25 robotic-assisted procedures (radical prostatectomies) using the validated d2 attention test (computer-assisted, Hogrefe test systems, Germany). Error frequency, work rate, and accuracy of task performance were evaluated as parameters of the fluctuation in concentration. Data were correlated with clinical parameters, including console times, positive surgical margin rates and the use of a nerve-sparing procedure. Pre- and post-operative test results revealed no differences in the number of items performed, but a significant decline in the error-corrected performance between the pre- and post-operative tests was observed with increasing console time (p = 0.046; median console time 123 min.). No differences in the pre-operative tests for consecutive procedures (mean time between procedures 93 min.) were found, whereas the number of errors (missed items) increased in the post-operative tests (p = 0.0025). The measured differences in test results showed no association with the positive surgical margin rate. A planned nerve-sparing procedure tended to result in a lower level of concentration found in pre-operative testing (p = 0.07). Concentration decrease and loss of attention during robotic-assisted procedures can be measured validly using the d2 attention test. Longer console times lead to loss of attention but consecutive procedures do not decrease the test or surgical performance. Further studies need to address whether similar effects apply to the comparable open or other robotic procedures or to different levels of surgeons experience.

[Retroperitoneal endometriosis : When a rare form of endometriosis becomes a urological disease]. / Retroperitoneale Endometriose : Wenn eine seltene Form der Endometriose zur urologischen Erkrankung wird.

BACKGROUND: Retroperitoneal endometriosis is a common benign disease, which requires an interdisciplinary approach. In the clinical practice diagnosis is often delayed for years after onset of the unspecific symptoms so that increased awareness is necessary for detection of the presence of the disease. OBJECTIVE: This article provides a description of the disease including the symptoms and pathogenesis, an introduction to the complexity of diagnostic investigations and the current therapy recommendations. MATERIAL AND METHODS: Comparison of current therapy recommendations according to the guidelines under consideration of individual studies and background research. Assessment of studies and the accompanying interpretations with the intention of presenting an introduction to the topic with therapy recommendations. RESULTS: From a urological point of view retroperitoneal endometriosis is a benign disease affecting the ureters and urinary bladder. Involvement of the ureters leading to hydronephrosis caused by ureteral compression represents an absolute indication for therapy. Recurrent macrohematuria can also necessitate treatment. Treatment includes surgical excision of the focal point of endometriosis as the first line therapy. Various operative procedures and access routes are available but when possible a minimally invasive procedure should be used. A second line drug therapy is also possible. CONCLUSION: Surgical excision of a clinically significant focus of endometriosis is the gold standard for therapy. This procedure should take place in a specialized center within an interdisciplinary consensus. Due to the fact that endometriosis is primarily a benign disease, medical clarification for the patient concerning the benefits and risks of therapy is absolutely necessary. An individual therapy concept under consideration of factors, such as the specific clinical relevance and psychological stress is recommended and in close cooperation with the patient.

Transurethral versus suprapubic catheter at robot-assisted radical prostatectomy: a prospective randomized trial with 1-year follow-up.

OBJECTIVE: To evaluate urethral catheter (UC) versus suprapubic tube (SPT) without stenting the anastomosis at robot-assisted radical prostatectomy (RALP) regarding surgical outcome and catheter-associated discomfort. One year after surgery, continence and patient satisfaction were evaluated. MATERIALS AND METHODS: Sixty-two patients undergoing RALP were prospectively randomized to urinary drainage with UC or with SPT. Functional results were assessed with standardized questionnaires (IPSS, IPSS Bother Score, IIEF and Visual Analogue Scale) preoperatively, after catheter removal and 1 year after surgery. Moreover, bother by the catheter as well as pain due to the catheter was assessed. RESULTS: At personal hygiene, SPT was significantly less bothersome on the day of surgery as well as POD 1-6. Pain caused by the catheter did not differ significantly between the two groups except for POD 5 and 6, when the SPT performed significantly better. Differences regarding voiding parameters after catheter removal did not reach statistical significance. One year after surgery, no significant difference between the two groups was found regarding urinary function and IPSS. Though not statistically significant either, the need for the incision of bladder neck contracture (BNC) in two patients in the UC group is of note, as in the SPT group, no BNC occurred. CONCLUSION: Draining the bladder with SPT only is a feasible option in patients undergoing RALP. Patients with SPT are significantly less bothered by the catheter at personal and genital hygiene compared to UC. The risk of BNC seems to be reduced in the SPT group.

Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a promising target for diagnostics and therapy of prostate carcinoma (PCa). Based on the hypothesis that PSMA expression can be modulated by variations in androgen deprivation therapy (ADT), we investigated the binding of a PSMA-directed radiopharmaceutical in vitro in order to get an insight of the interactions between altered premedication and PSMA expression before repetitive PSMA-directed PET/CT for therapy response and targeted therapy implementation. METHODS: The human castration-resistant PCa cell line VCaP (CRPC) was treated with either 1 nmol/L testosterone (T) over 20 passages yielding the androgen-sensitive cell line (revCRPC) or with 5 µmol/L abiraterone acetate (AA) generating the abiraterone-tolerant subtype CRPCAA. In these cell lines, T and AA were varied by either supply or withdrawal of T and AA. PSMA expression of the three cell culture models was detected by Western blot and immunohistochemical staining. For quantitative measurement of tracer uptake, 0.3 nmol/L (68)Ga-labelled PSMA-HBED-CC peptide (100-300 kBq/ml) was added to different treated parallel cultures (n = 9 each). Time-dependent uptake per 10(6) cells of each culture was calculated and evaluated. PSMA mRNA expression was investigated by qPCR. RESULTS: PSMA expression increased dependently on intensified ADT in all three basic cell lines. (68)Ga-PSMA-HBED-CC uptake almost doubled during 3 h in all cell lines (p < 0.01). Compared to the basic cells, pre-incubation with abiraterone for 48 h resulted in a significant increased uptake in CRPC (p < 0.001). In revCRPC, 48-h AA pre-incubation resulted in an eightfold higher uptake after 3 h (p < 0.001). Additional withdrawal of external testosterone increased the uptake up to tenfold (p < 0.01). The increase of PSMA expression upon ADT and AA treatments was confirmed by qPCR and Western blot data. Furthermore, in CRPCAA, 48-h AA withdrawal increased the uptake up to fivefold (p < 0.01). CONCLUSIONS: The investigated three PCa cell culture subtypes represent a serial preclinical model of androgen deprivation therapy as a proxy for clinical situations with differing basal PSMA expression. The uptake of PSMA-binding tracers could be stimulated by therapeutic effective short-term variation in premedication in all stages of ADT response. These complex interactions have to be considered in the interpretation of diagnostic imaging using PSMA ligands as well as in the optimal timing of PSMA-based therapies.

Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography.

BACKGROUND: The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by (68)Ga-PSMA PET/CT. METHODS: Retrospective analysis of 35 PCa patients underwent (68)Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS: Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS: This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by (68)Ga-PSMA PET/CT. The use of (68)Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

[Antibiotic resistance in nontyphoidal salmonellae serovars in the Czech Republic]. / Antibiotická rezistence u netyfových sérovaru Salmonella spp. v Ceské republice.

STUDY AIM: To determine antibiotic resistance and incidence of multidrug resistance among Nontyphoidal salmonellae serovars isolated from humans. MATERIAL AND METHODS: Consecutive Salmonella isolates from patients, recovered in 48 microbiology laboratories in May 2012, were analyzed in the respective reference laboratories at the National Institute of Public Health. Strains were re-identified and differentiated into serovars. Their minimum inhibitory concentrations (MICs) to 11 antibiotics were determined by the microdilution method. RESULTS: Of 25 serovars identified among 637 strains of Salmonella enterica, the most frequent were Enteritidis (87.0 %), Typhimurium (4.9 %), and monophasic Typhimurium 4,[5],12:i:- (2.0 %) and Mbandaka (0.6 %); other serovars were rare. Altogether 558 strains (87.6 %) were susceptible to all antibiotics tested and the remaining 79 strains were resistant to one or more antibiotics. The prevalence rates of resistance to individual antibiotics among 637 study strains were as follows: ampicillin 8.5%, tetracycline 5.7%, sulfamethoxazole 5.2%, cipro-floxacin 3.8%, and chloramphenicol 2.5%. Resistance to gentamicin, trimethoprim, and third and fourth generation cephalosporins was rare ( 0.5%) and none of the study strains showed resistance to meropenem. Three producers of extended spectrum beta-lactamase were multidrug resistant and two of them recovered from twins exhibited a different pattern of resistance. Resistant strains were most often assigned to the following serovars: Enteritidis (49.4%), Typhimurium (26.6%), and monophasic Typhimurium (15.2%). While only 7% (39 of 554 strains) of Enteritidis strains were resistant, the serovars Typhimurium and its monophasic variant 4,[5],12:i:- showed high rates of resistance, i.e. 66.7 and 92.3%, respectively. Furthermore, resistance was revealed in all strains of the serovars Virchow (n = 3), Kentucky (n = 1), and Newport (n = 1), in two of three strains of the serovar Infantis, and in one of two strains of the serovar Stanley. All five blood isolates were assigned to the serovar Enteritidis and one of them showed resistance to ciprofloxacin. Of 79 resistant strains, 26.6% showed resistance to ampicillin only and 24.1% to ciprofloxacin only, with multidrug resistance, i.e. resistance to three or more antibiotics, confirmed in 43.0% of strains. CONCLUSION: Despite a relatively low prevalence of resistance to the antibiotics tested among 637 study strains, the following alarming findings were made: Detection of Salmonella enterica strains resistant to ciprofloxacin as the drug of choice or to higher generation cephalosporins and multidrug resistance revealed in two thirds of the strains of the serovar Typhimurium and in all but one strains of its monophasic variant 4,[5],12:i:-.

Prediction of outcome in patients with urothelial carcinoma of the bladder following radical cystectomy using artificial neural networks.

AIM: The outcome of patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) shows remarkable variability. We evaluated the ability of artificial neural networks (ANN) to perform risk stratification in UCB patients based on common parameters available at the time of RC. METHODS: Data from 2111 UCB patients that underwent RC in eight centers were analysed; the median follow-up was 30 months (IQR: 12-60). Age, gender, tumour stage and grade (TURB/RC), carcinoma in situ (TURB/RC), lymph node status, and lymphovascular invasion were used as input data for the ANN. Endpoints were tumour recurrence, cancer-specific mortality (CSM) and all-cause death (ACD). Additionally, the predictive accuracies (PA) of the ANNs were compared with the PA of Cox proportional hazards regression models. RESULTS: The recurrence-, CSM-, and ACD- rates after 5 years were 36%, 33%, and 46%, respectively. The best ANN had 74%, 76% and 69% accuracy for tumour recurrence, CSM and ACD, respectively. Lymph node status was one of the most important factors for the network's decision. The PA of the ANNs for recurrence, CSM and ACD were improved by 1.6% (p = 0.247), 4.7% (p < 0.001) and 3.5% (p = 0.007), respectively, in comparison to the Cox models. CONCLUSIONS: ANN predicted tumour recurrence, CSM, and ACD in UCB patients after RC with reasonable accuracy. In this study, ANN significantly outperformed the Cox models regarding prediction of CSM and ACD using the same patients and variables. ANNs are a promising approach for individual risk stratification and may optimize individual treatment planning.

External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). METHODS AND METHODS: Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5. RESULTS: The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p-values <0.001). CONCLUSIONS: We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC.

[Validation of pre-cystectomy nomograms for the prediction of locally advanced urothelial bladder cancer in a multicentre study: are we able to adequately predict locally advanced tumour stages before surgery?]. / Validierung von Präzystektomienomogrammen zur Vorhersage lokal fortgeschrittener Harnblasenkarzinome in einer multizentrischen Studie : Können wir lokal fortgeschrittene Tumorstadien präoperativ ausreichend sicher vorhersagen?

OBJECTIVE: Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement. MATERIALS AND METHODS: Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages. RESULTS: Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours. CONCLUSIONS: The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.

[Influence of older age on survival after radical cystectomy due to urothelial carcinoma of the bladder: survival analysis of a German multi-centre study after curative treatment of urothelial carcinoma of the bladder]. / Einfluss des Alters auf das karzinomspezifische Überleben nach radikaler Zystektomie : Überlebensanalyse aus einer deutschen Multicenterstudie nach kurativer Therapie eines Urothelkarzinoms der Harnblase.

BACKGROUND: The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients <75 and >75 years of age (median follow-up was 42 months). PATIENTS AND METHODS: Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed. RESULTS: The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p<0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p<0.001) and CSS (HR=1.27; p=0.018). CONCLUSIONS: An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

[Patients with bladder cancer in clinical stage T2 : survival benefit of downstaging in comparison to patients with confirmed muscle invasion in cystectomy specimens]. / Harnblasenkarzinompatienten im klinischen Tumorstadium T2 : Überlebensvorteil eines Downstaging gegenüber Patienten mit bestätigter Muskelinvasion im Zystektomiepräparat.

BACKGROUND: Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy. MATERIALS AND METHODS: Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging. RESULTS: A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence. CONCLUSION: Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.

Antisense anti IGF-I cellular therapy of malignant tumours: immune response in cancer patients.

The treatment of cancer by antisense anti-IGF-I cellular therapy inducing immune response has evoked interest among many promising strategies. Here, we reported some results obtained from patients with cancer, mainly glioblastoma treated by this strategy, which was also extended to patients with colon carcinoma, ovary cystadenocarcinoma and prostate adenocarcinoma. It was shown that, in the phase I of clinical trial, patients vaccinated with their own tumour cells treated by antisense IGF-I presented a slight increase of temperature. Their peripheral blood lymphocytes showed a shift in the percentage of CD8 effector cells as judged by expression of cell surface markers CD8+ CD28+. Particularly, in two treated patients with glioblastoma, the survival time was 19 and 24 months respectively in comparison to the range of 12 to 15 months observed in the case of classical treatment such as surgery, radiation or chemotherapy. These results, although preliminary, gave indication that the reported strategy could deserve consideration owing to its safety. Furthermore, the increase in the percentage of peripheral blood monomorphonucleated cells (PBMNCs) with effector phenotype, i.e., CD8+ CD28+ in vaccinated patients might explain their prolonged survival time.

Complementary therapies for cancer patients: assessing information use and needs.

Many cancer patients seek complementary therapies (CTs) for cancer management; however, relatively little is known about patients' CT information seeking behaviour. Therefore, we assessed: 1) cancer patients' use of the types and sources of CT information; 2) their information preferences; and 3) their understanding of the phrase "scientific evidence or proof that a therapy works." We collected data from 404 patients attending the Tom Baker Cancer Centre (TBCC) in Calgary and 303 patients calling the Cancer Information Service (CIS) helpline. In most cases, patients wanted information on the safety of CTs, how CTs work and their potential side effects. Physicians and conventional cancer centres were the most desired sources of CT information, but relatively few patients obtained information via these sources. Although patients were aware of the meaning of scientific evidence, they often used information based on non-scientific evidence, such as patient testimonials. The creation of a supportive care environment in conventional cancer treatment centres, by providing CT information, may help address cancer patients' concerns and alleviate some of the stress that may have been caused by the cancer diagnosis.

[Medical treatment of metastatic renal cell carcinoma after the approval and market entry of multitargeted tyrosine kinase inhibitors in Germany]. / Medikamentöse Therapie des metastasierten Nierenzellkarzinoms: eine Standortbestimmung nach Einführung der Multi-Tyrosinkinaseinhibitoren in Deutschland.

PURPOSE: To describe the current use and administration of multitargeted tyrosine kinase inhibitors (sunitinib and sorafenib) in the management of metastatic renal cell carcinoma (RCC) and to characterise frequent adverse events. MATERIALS AND METHODS: A questionnaire was sent to 104 urologists and medical oncologists having their own practice. The common use of medical treatment with sunitinib and sorafenib in patients with metastatic RCC was recorded. Data on the most frequent drug-associated adverse events were registered and described in a preliminary patient cohort. RESULTS: Medical oncologists in private practice treat over twice as many patients with metastatic RCC (8/year) as established urologists. Most medical oncologists but not urologists already use multitargeted tyrosine kinase inhibitors. For the initiation of treatment, most urologists admit patients to a hospital, whereas medical oncologists start and carry out medical treatment themselves. In all patients adverse events occurred due to medical treatment, leading to therapy stop or pause in 53% of patients. The most frequent adverse events were abnormal fatigue, arterial hypertension, diarrhoea and the hand-foot skin syndrome. CONCLUSIONS: Multitargeted tyrosine kinase inhibitor therapy in Germany is currently done predominantly by medical oncologists rather than urologists. Adverse events caused by sunitinib and sorafenib frequently required medical care, and in our initial series of patients prompted physicians to pause treatment.

[Complications and side effects of low dose rate brachytherapy for the treatment of prostate cancer: data on a 13 year follow-up study from Mannheim]. / Komplikationen und Nebenwirkungen der LDR-Brachytherapie beim Prostatakarzinom : 13-Jahresdaten aus Mannheim.

BACKGROUND: Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis. MATERIAL: A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated. RESULTS: The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time. CONCLUSION: BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.

[Relevance of the neuroendocrine differentiation in prostatic carcinoma]. / Bedeutung der neuroendokrinen Differenzierung im Prostatakarzinom.

BACKGROUND: NE tumor cells are present in virtually all prostatic adenocarcinomas. As they express no androgen receptor they are hormone independent. During anti-androgenic therapy their number increases. Their prognostic value is controversial. MATERIAL AND METHODS: In 233 patients with prostatic carcinoma the NE differentiation was determined in a hot spot (7.9 mm(2)) with maximum CgA positive cell density. A high NE differentiation (HNE) was defined by a least 30 NE tumor cells, while less means a low NE differentiation (LNE). In addition the occurrence of NE tumor cells was defined as solitary or clustered (> or =5 NE tumor cells in close proximity). RESULTS: In advanced and high grade tumors more and clustered NE tumor cells could be found than in low grade and organ confined tumors. Moreover HNE tumors and occurrence of NE clusters resulted in a significant shorter progression-free interval. CONCLUSIONS: Besides the quantity of NE differentiation the quality of the growth pattern of NE tumor cells is of relevance in prostatic carcinoma.

[Current aspects of stone therapy]. / Aktuelle Aspekte der Steintherapie.

More than 30 % of all admissions to an urologic clinic are for the treatment of urinary stones. In almost all cases, the treatment is minimally invasive employing extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS) or percutaneous nephrolithotomy (PCNL). Technical advances in endourology and a growing expertise in ESWL led to a decline in ESWL and an increase in endoscopic techniques. In comparison with ESWL, the endoscopic techniques are more invasive but in most cases achieve a stone free state faster. With the introduction of diagnosis related groups (DRG), the economic aspect of stone therapy is gaining in importance. Stone prevention leads to a cost reduction in the health care system, justifying the use of an appropriate stone metaphylaxis. This review article presents the current recommendations for interventional urinary stone therapy and lists the options of conducting both medical and economically rational therapy.