Does visualisation during urethrocystoscopy provide pain relief? Results of an observational study.

BACKGROUND: To measure the effects of real-time visualisation during urethrocystoscopy on pain in patients who underwent ambulatory urethrocystoscopy. METHODS: An observational study was designed. From June 2012 to June 2013 patients who had ambulatory urethrocystoscopy participated in the study. In order to measure pain perception we used a numeric rating scale (NRS) 0 to 10. Additional data was collected including gender, reason for intervention, use of a rigid or a flexible instrument and whether the patient had had urethrocystoscopy before. RESULTS: 185 patients were evaluated. 125 patients preferred to watch their urethrocystoscopy on a real-time video screen, 60 patients did not. There was no statistically relevant difference in pain perception between those patients who watched their urethrocystoscopy on a real-time video screen and those who did not (p = 0.063). However, men who were allowed to watch their flexible urethrocystoscopy experienced significantly less pain, than those who did not (p = 0.007). No such effects could be measured for rigid urethrocystoscopy (p = 0.317). Furthermore, women experienced significantly higher levels of pain during the urethrocystoscopy than men (p = 0.032). CONCLUSIONS: Visualisation during urethrocystoscopy procedures in general does not significantly decrease pain in patients. Nevertheless, men who undergo flexible urethrocystoscopy should be offered to watch their procedure in real-time on a video screen. To make urethrocystoscopy less painful for both genders, especially for women, should be subject to further research.

Pelvic exenteration for recurrent or advanced gynecologic malignancies - Analysis of outcome and complications.

Pelvic exenterations are known to be a last resort therapeutic option for advanced or recurrent gynecologic malignancies, which are known to have poor prognosis. All women treated with anterior (APE) or total (TPE) pelvic exenteration at our University hospital within a five-year period were identified and their data retrospectively analysed. Parameters such as demographic information, tumor type and stage, previous therapy as well as complication rate and overall survival were evaluated. 47 women were enrolled in this study. Most common indication for PE was cervical cancer (51.1%) followed by carcinoma of the vagina (17%), vulva (10.6%), endometrium (8.5%), ovaries (4.3%) and uterus (2.1%). Patients had received 1, 2 or 3 treatment modalities prior in 12.8%, 38.8% and 21.2% respectively. Predominant urinary diversion was ileum conduit (75.5%). Major complications (Clavien Dindo ≥ III) were observed in 40.4%, none in 19.2%. Early mortality was 4.3%. Median Overall Survival (mOS) was 14 months with 2- and 3-year survival rates of 38.8% and 21.2% respectively. After a median follow up of 47 months, 25.5% were still alive. Excluding patients with metastatic disease (n = 10), mOS was 20.6 months with 2- and 3-year survival rates of 46% and 35.2%. OS was significantly worse for patients with positive margins (p = 0.003). Receiving neoadjuvant treatment (25.5%) correlated with negative margins (p = 0.013) but not with overall survival. PE is feasible with acceptable complication and mortality rates. The long-time benefit is notable bearing in mind the extensive nature of the malignancies and the procedure undertaken.

[Transoral vertebroplasty: an alternative for operative treatment of metastases of the upper cervical spine]. / Die transorale Vertebroplastie: Eine Alternative in der operativen Behandlung von Metastasen der oberen HWS.

Analogue to the demographic changes and the accompanying increased incidence of tumorous diseases, the number of patients with metastatic bone tumors of the spine is also increasing. Metastatic bone tumors are the most significant cause of pain in cancer patients. Pain and instability are the main indications for surgery. Minimally invasive procedures are recommended in patients with a poor medical condition and with a poor prognosis.Transoral vertebroplasty can be successfully used to reduce pain and provide stability in the palliative treatment of metastases of the vertebral axis. This procedure has the advantage of providing rapid pain relief and spinal stabilization.The operative technique is described and discussed with reference to the current literature. As an example the case of a 67-year-old patient is described, who was suffering from prostate cancer and a painful metastasis of the dens axis. After interdisciplinary consensus, transoral vertebroplasty was performed. The procedure was effective in achieving pain relief and providing stability and 7 months after the operation no further spinal metastases had occurred.

[Immunostimulatory CpG oligodeoxynucleotides (CpG-ODN) in an orthotopic murine transitional cell carcinoma (TCC) model. Effect on local cytokine expression]. / Immunstimulative CpG-Oligodeoxynukleotide (CpG-ODN) im orthotopen murinen Transitionalzellkarzinom (TCC)-Modell. Effekt auf die lokale Zytokinexpression.

CpG-oligodeoxynucleotides (CpG-ODN) are potent stimulators of the innate immune system. They promote a Th1-biased immune response with antineoplastic potential. We recently demonstrated antitumoral effects of CpG-ODN in murine transitional cell carcinoma (TCC) models. The purpose of the present work was to more precisely define the immunological nature of this immunotherapeutic approach to TCC.MB-49 TCC was established in female C57/Bl6 mice by intravesical tumor cell instillation after poly-L-lysine conditioning of the bladder (day 0) as described previously. Three groups of six mice were treated: intravesical instillation of 50 microl PBS on days 1, 3, 5, and 7 (group 1, untreated control); 10 nmol CpG 1668 on days 1, 3, 5, and 7 (group 2); and 10 nmol GpC 1668 on days 1, 3, 5, and 7 (group 3). Six native bladders served as no-treatment/no-tumor controls (group 4). Mice were sacrificed on day 11; bladders and draining lymph nodes were removed, and mRNA was prepared for quantitative real-time polymerase chain reaction. Samples were analyzed on a Bio-Rad iCycler for IL 10, TGF-beta, IL 12, and IFNgamma expression; threshold values were compared to beta-actin as housekeeping gene.Tumor take was 100%. Three animals in group 1 had to be sacrificed in advance due to rapid tumor progression. Relative cytokine expression was comparable in groups 1 and 4. IL-10, IL-12, TGF-beta, and IFNgamma were overexpressed in groups 2 and 3. CpG-ODN treatment of murine TCC results in overexpression of both classic Th1 cytokines (IL 12 and IFNgamma) and the Th2 marker IL 10. TGF-beta expression is increased as well. These phenomena are not induced by the growing TCC but by CpG-ODN therapy. They are accompanied by an objective clinical response, as we were able to show recently. Immunostimulatory DNA holds promise to be a novel therapeutic agent in TCC.

[Gender-specific characteristics and survival of renal cell carcinoma]. / Geschlechtsspezifische Charakteristika und Prognose des Nierenzellkarzinoms.

BACKGROUND: Renal cell carcinoma (RCC) occurs twice as often in men as in women; however, the influence of gender on stage, grade, subtype and prognosis has not been studied in detail. METHODS: This study included 780 patients treated by (partial) nephrectomy at our institution in Marburg between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Of the 780 patients, 486 (62%) were men and 294 (38%) were women. Women were significantly older (mean, 65.3 vs. 62.2 years; p<0.001, t-test), presented at lower T stages (p=0.046, chi(2)) and suffered metastasis less frequently at diagnosis (p=0.026, chi(2)). In addition, women more frequently had clear cell tumours (85.2% vs. 78.3%) and less frequently papillary tumours (11.0% vs. 18.8%) than men (p=0.026, chi(2)). In contrast, men had an increased risk of death from RCC (HR 1.23, CI 0.92-1.63); Kaplan-Meier curves revealed a significant difference in tumour-specific survival between men and women (p=0.033, log rank; 5-year survival 74% vs. 83%). However, unlike tumour stage and tumour grade, gender could not be retained as a significant independent prognostic marker in multivariate analysis. CONCLUSION: In general, RCC in men is characterized by higher tumour stages and more frequent metastasis at diagnosis along with inferior tumour-specific survival. However, as gender failed to qualify as an independent prognostic marker for tumour-specific survival, delayed diagnosis due to insufficient routine medical check-up and/or a more aggressive tumour biology might be be a concurrent cause. Thorough regular medical check-ups for men, also with regard to RCC, are thus mandatory.

[Transitional cell carcinoma of the bladder. Evaluation of plasma levels of cellular fibronectin as a stage-dependent marker]. / Das Transitionalzellkarzinom der Harnblase. Evaluation von zellulärem Fibronektin im Plasma als stadienabhängiger Marker.

Up to now markers for transitional cell carcinoma of the bladder (TCC) are missing. Fibronectin (FN) seems to play a key role in progression and invasion of malignant tumors. The aim of this study was to assess the value of cellular FN (cFN), a more specific subform of produced FN, in different stages of TCC.cFN was determined using a highly sensitive immunoassay which we developed. Blood samples were taken of 45 patients with the first diagnosis of TCC before undergoing TUR-B and 6 patients with metastatic TCC before chemotherapy; 70 patients with nonmalignant urological disorders served as a control group.Patients with TCC showed significantly elevated cFN plasma levels compared to controls (p<0.05). Patients with muscle-invasive disease (n=15) showed significantly higher cFN plasma levels compared to the group with superficial TCC. Patients with metastatic TCC showed the highest, but not significantly elevated cFN plasma levels compared to patients with muscle-invasive TCC.The elevated cFN plasma levels in TCC underline the important role of cFN for tumor progression and its potential role as a marker for TCC. Upcoming investigations are necessary to prove the value of the potential marker cFN during follow-up and its impact as a prognostic factor for recurrence and progression of TCC.

[Follow-up of bladder cancer : The right examinations at the right time]. / Tumornachsorge des Harnblasenkarzinoms : Die richtigen Untersuchungen zum richtigen Zeitpunkt.

Schedules for the follow-up (FU) of bladder cancer patients are predominantly based on studies with low level of evidence and the resulting guidelines' recommendations that are often founded on expert consensus. FU of non-muscle invasive bladder cancer (NMIBC) includes cystoscopy and cytology as standard, and imaging modalities to a lower extent. FU of muscle-invasive bladder cancer (MIBC) depends primarily on the therapeutic modality chosen and on the stage of disease. In this scenario, FU is complemented by functional and quality of life related aspects. These apply even more for FU in palliative situations. Here, the individual focus is on examinations that might have a consequence in terms of survival and/or symptom relief.

[Cystitis emphysematosa--a case report]. / Emphysematöse Zystitis : Ein Fallbericht.

We present a rare case of cystitis emphysematosa in an 85-year-old female patient in whom the typical risk factors were present: diabetes of long standing, neurogenic bladder and urinary infection with E.coli. Thanks to early diagnosis by cystoscopy and abdominal CT, after antibiotic treatment, appropriate insulin therapy and continuous bladder drainage the course was uneventful. The patient was fit to leave hospital after 14 days.

Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches.

OBJECTIVES: Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10-35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment. MATERIALS AND METHODS: This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity. RESULTS: Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy. CONCLUSIONS: Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.

[Second-line thalidomide/IL-2 therapy in metastatic kidney cancer--results of a pilot study]. / Thalidomid/Interleukin-2 in der Second-line-Therapie des metastasierten Nierenzellkarzinoms--Ergebnisse einer Pilotstudie.

PURPOSE: On the basis of promising first-line data we have evaluated the safety and efficacy of a combination therapy comprising interleukin-2 (IL-2) and thalidomide in patients with metastatic renal cell carcinoma (RCC) refractory to both immuno- and chemotherapy. PATIENTS AND METHODS: 14 patients with progressive metastatic RCC, in whom prior immunochemotherapy had failed but who desired further active therapy, were enrolled in this study. Oral thalidomide was started at 200 mg/d and escalated after two days to 400 mg/d at week 0. IL-2 at 7 MIU/m (2) was given by subcutaneous injection, starting at week 1, days 1 to 5, weeks 1 to 4, with no IL-2 at weeks 5 and 6. The response was assessed every other therapy cycle. RESULTS: 12 patients were evaluable for response. There was no objective response; 4 patients showed stable disease for 21, 15, 13 and 9 months, respectively. Toxicities were predominantly grade 1 - 3 and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after seven weeks due to increasing confusion. 11 patients required IL-2 dose reduction. Time on therapy ranged from 3 - 44 weeks (median, 19 weeks). Median overall survival was 22 months. Up to date, all patients have discontinued treatment. CONCLUSIONS: We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable and the clinical benefit is uncertain. Therefore thalidomide/IL-2 may not represent a promising therapeutic approach for this subgroup of patients.

[Renal and ureteral injuries. Diagnosis and treatment]. / Nieren- und Ureterverletzungen. Diagnostik und Therapie.

BACKGROUND: In severely injured patients, urologic trauma is diagnosed in about 10 % of patients. Renal trauma is most common, while ureteral trauma is in the majority of cases iatrogenic. These two urologic injuries influence the clinical course, morbidity, and mortality. Thus, rapid identification, sufficient diagnostic workup, and adequate therapy of renal and ureteral injuries are essential. THEME: This article reviews the actual diagnostic procedures, classification, and stage-dependent therapy options in renal and ureteral injuries.

[News with clinical relevance from major scientific meetings 2015--Update Urooncology]. / Was gab es Neues auf den Kongressen 2015?--Update Uroonkologie.

What new developments in urooncology were discussed at the 2015 annual meetings of ASCO, EAU, DGU and ESMO? This review summarises news relevant to the daily diagnosis and treatment of prostate, bladder and kidney cancer. While study results seem to change paradigms in the treatment of prostate cancer, particularly in metastatic but still hormone-sensitive stages, immunotherapeutic strategies for the treatment of kidney and urothelial cancer are very promising and might expand the systemic therapeutic options in the years to come.

[Big surprise in the lesser pelvis]. / Große Überraschung im kleinen Becken.

A 17-year-old young man presented at our clinic with asymptomatic microhematuria. Ultrasonography and computer tomography found an intraperitoneal lesion of unknown dignity located on top of the bladder. Surgical exploration and histological examination confirmed the diagnosis of a secondary pelvic spleen, a lien bipartitus.

[Operative interventions of urologic traumata in severe injured patients in the acute phase]. / Operative Interventionen urologischer Verletzungen beim schwerverletzten Patienten in der Akutphase.

INTRODUCTION: The frequency of urological traumata and the need for interventions in severely injured patients in Germany are unknown. The aim of this study was to determine the frequency of urological traumata in about 90,000 severely injured patients (Injury Severity Score, ISS ≥ 16). MATERIALS AND METHODS: Data of 90,000 patients from the TraumaRegister DGU® were retrospectively analyzed. All patients with an ISS of ≥ 16 were included. The kind of urological traumata and the need for urological intervention within 24 hours were assessed, as well as the kind of accident, additional traumata and the clinical course. RESULTS: 48,797 patients fulfilled the inclusion criteria. Urological trauma was existent in 7.1 %, especially in men (78 %). Kidneys were affected most frequently (4.8 %) compared to ureters (0.2 %), urinary bladder (1.2 %), urethra (0.5 %) and genitals (0.4 %). Traffic accidents and falls from higher levels represented the main cause for urological traumata (> 90 %). It was associated with additional pelvis, thorax and abdomen traumata (each 7.1 %) and showed a distinct increase dependent on the abbreviated injury scale (AIS). Ureter (10.6%) and urethra (6.3%) trauma was deferred diagnosed most, this was associated with a higher rate of urological operations. The general duration of hospital stay and that in the intensive care unit were prolonged by urological traumata. DISCUSSION: The data showed the prevalence of urological trauma in severely injured patients analyzed in a huge patient cohort of the TraumaRegister DGU®. For the first time the number, degree and medical care in the reality of urological traumata in severely injured patients were available.

[News with clinical relevance from major scientific meetings 2014 - Update Urooncology]. / Was gab es Neues auf den Kongressen 2014? - Update Uroonkologie.

What is new in urooncology in the year 2014? This review gives a brief but comprehensive overview of new developments in diagnosis and treatment of localized as well as advanced prostate, bladder and kidney cancer which have been presented on the occasion of the annual meetings of the European and American urologic and oncological associations in 2014. Attention is particularly directed to those data and results from trials which might be of direct or indirect clinical relevance.

[Indications for nephron-sparing surgery. Analysis over a 13-year period in the context of changing guidelines]. / Indikationsstellung zur organerhaltenden Nierentumorchirurgie. Analyse eines 13-Jahres-Zeitraums vor dem Hintergrund sich wandelnder Leitlinien.

BACKGROUND: The indications for nephron-sparing surgery have been considerably extended by guideline recommendations in recent years. It remains unclear whether clinical practice still reflects these new guidelines. OBJECTIVE: In this retrospective, monocentric analysis at a tertiary referral center the indications for partial nephrectomy over a 13-year period were evaluated. METHODS: In a retrospective database analysis all cases of surgically treated renal masses from 2001 to 2013 were evaluated. Besides demographic, tumor-specific and perioperative variables the development of the surgical technique depending on the tumor stage was evaluated. RESULTS AND DISCUSSION: The proportion of nephron-sparing surgery cases increased from below 20 % in 2001 to 35 % in 2013 in the entire cohort. For stage T1a tumors, partial nephrectomy increased from approximately 50 % to over 90 % and for T1b tumors it rose from 10 % to 50 %. Logistic regression revealed stage 1 tumors to be predictive of partial nephrectomy over the complete evaluation period. Extending the indications for partial nephrectomy even to higher stages is under discussion but not yet supported by data from prospective, controlled studies.

[Metastasized renal cell carcinoma. Measurement of plasma levels of the tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib]. / Metastasiertes Nierenzellkarzinom. Bestimmung der Plasmaspiegel der Tyrosinkinaseinhibitoren Sunitinib, Sorafenib und Pazopanib.

BACKGROUND: Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry. RESULTS: The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals. CONCLUSION: Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.

Radiommunological measurement of leptin in plasma of obese and diabetic human subjects.

Studies in mice have identified the ob gene product, leptin, as a signaling factor regulating body weight homeostasis and energy balance. Defective production of the encoded protein may be one of the causes for the development of obesity. Using a high affinity antibody, that in immunohistochemical studies specifically stained human adipocytes, a radioimmunoassay was established and leptin immunoreactivity was quantified in plasma of lean and obese human subjects. Chromatographic analysis suggested that the immunoreactive material in plasma is identical to that found in extracts from human fat and represent a protein with a molecular size of approximately 16 kD. Fasting levels were measured in plasma of 75 lean and obese human subjects (body mass index (BMI) 17.7 - 87.3). The mean concentration of leptin in plasma of lean subjects (BMI < or = 28) was 69.3 +/- 36.9 fmol/ml plasma (mean +/- SD, n=27). The highest concentration measured in obese was 533.3 fmol/ml plasma. The levels showed a strong positive correlation with BMI (r=0.77, p<0.001). A subgroup of diabetic patients did not significantly differ in their leptin plasma levels from non-diabetic subjects with similar BMI.

A prospective open-label single-arm phase II study of chimeric monoclonal antibody cG250 in advanced renal cell carcinoma patients.

cG250 is an IgG1 kappa light-chain chimeric monoclonal antibody that binds to a cell surface antigen found on 95% of clear-cell renal cancer. A multicentre phase II study was performed to evaluate the safety and efficacy of repeated doses of cG250. Thirty-six patients with metastatic RCC were included. All patients were nephrectomized for the primary tumour. Twenty-one patients were pretreated (e.g. with IL-2, IFN-alpha). A weekly dose of 50 mg cG250 was given by i.v. infusion for 12 weeks. Patients with SD or tumour response (PR, CR) after 12 weeks of treatment could receive additional treatment for 8 more weeks. None of the 36 enrolled patients had any cG250 grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. ELISA testing gave no evidence for relevant amounts of HACA. Eleven patients presented with SD and ten were eligible for extension treatment. After the end of the study in the follow-up period, one patient demonstrated a CR in week 38 and another patient with SD showed a significant reduction of the overall tumour load in week 44. Six additional patients with progressive disease at study entry were stable for more than six months after the treatment start. The weekly schedule of i.v. cG250 in patients with metastatic RCC was safe, very well tolerated and non-immunogenic in a 12-week treatment regimen. cG250 showed anti-tumour activity.

[Reconstructive surgical therapy of infected pilonidal sinus]. / Plastisch-chirurgisches Therapiekonzept des infizierten Sinus pilonidalis.

INTRODUCTION: Infected sinus pilonidalis is common in young patients, causing much discomfort. Up to now, many different therapy options have been described. The aim of this study was to evaluate the longterm results for infected pilonidal sinus disease after primary drainage of the abscess, secondary rhomboid excision, and Limberg flap procedure. METHODS: 38 patients (5 female, 33 male, mean age 27,mean BMI 26.7 kg/m(2)) suffering from infected pilonidal sinus were first treated by incision of the abscess. After control of the inflammation (8-14 days), radical excision of the pilonidal sinus and defect closure by the Limberg flap procedure were performed. RESULTS: Two patients (5.2%) developed seroma and two (5.2%) developed infected hematoma. During follow-up, one patient (2.6%) showed recurrence. In 33 (87%), postoperative course and follow-up were uneventful (mean 23 months, range 1-36). The mean length of hospital stay was 3.2 days (range 1-4). CONCLUSIONS: In infected sinus pilonidalis disease, primary drainage of the abscess by incision, secondary radical rhomboid excision, and the Limberg flap procedure to close the defect can be recommended as a good therapeutic option due to its low complication rate, acceptable long-term results, and simple operative technique.